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Sample records for neurodevelopmental effects exist

  1. Neurobehavioral and neurodevelopmental effects of pesticide exposures

    NARCIS (Netherlands)

    London, L.; Beseler, C.; Bouchard, M.F.; Bellinger, D.C.; Colosio, C.; Grandjean, P.; Harari, R.; Kootbodien, T.; Kromhout, H.|info:eu-repo/dai/nl/074385224; Little, F.; Meijster, T.; Moretto, A.; Rohlman, D.S.; Stallones, L.

    2012-01-01

    The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and

  2. Neurobehavioral and neurodevelopmental effects of pesticide exposures

    DEFF Research Database (Denmark)

    London, Leslie; Beseler, Cheryl; Bouchard, Maryse F

    2012-01-01

    The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective ...

  3. Neurobehavioural and neurodevelopmental effects of pesticide exposures

    Science.gov (United States)

    London, Leslie; Beseler, Cheryl; Bouchard, Maryse F.; Bellinger, David C.; Colosio, Claudio; Grandjean, Philippe; Harari, Raul; Kootbodien, Tahira; Kromhout, Hans; Little, Francesca; Meijster, Tim; Moretto, Angelo; Rohlman, Diane S.; Stallones, Lorann

    2012-01-01

    The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and neurodevelopmental outcomes amongst occupational (both adolescent and adult workers) and non-occupational populations (children). The symposium discussion highlighted many challenges for researchers concerned with the prevention of neurotoxic illness due to pesticides and generated a number of directions for further research and policy interventions for the protection of human health, highlighting the importance of examining potential long-term effects across the lifespan arising from early adolescent, childhood or pre-natal exposure. PMID:22269431

  4. Neurodevelopmental Effects of Early Deprivation in Postinstitutionalized Children

    Science.gov (United States)

    Pollak, Seth D.; Nelson, Charles A.; Schlaak, Mary F.; Roeber, Barbara J.; Wewerka, Sandi S.; Wiik, Kristen L.; Frenn, Kristin A.; Loman, Michelle M.; Gunnar, Megan R.

    2010-01-01

    The neurodevelopmental sequelae of early deprivation were examined by testing (N = 132) 8- and 9-year-old children who had endured prolonged versus brief institutionalized rearing or rearing in the natal family. Behavioral tasks included measures that permit inferences about underlying neural circuitry. Children raised in institutionalized…

  5. Neurodevelopmental effects in children associated with exposure to organophosphate pesticides: A systematic review

    Science.gov (United States)

    Muñoz-Quezada, María Teresa; Lucero, Boris A.; Barr, Dana B.; Steenland, Kyle; Levy, Karen; Ryan, P. Barry; Iglesias, Veronica; Alvarado, Sergio; Concha, Carlos; Rojas, Evelyn; Vega, Catalina

    2013-01-01

    Many studies have investigated the neurodevelopmental effects of prenatal and early childhood exposures to organophosphate (OP) pesticides among children, but they have not been collectively evaluated. The aim of the present article is to synthesize reported evidence over the last decade on OP exposure and neurodevelopmental effects in children. The Data Sources were PubMed, Web of Science, EBSCO, SciVerse Scopus, SpringerLink, SciELO and DOAJ. The eligibility criteria considered were studies assessing exposure to OP pesticides and neurodevelopmental effects in children from birth to 18 years of age, published between 2002 and 2012 in English or Spanish. Twenty-seven articles met the eligibility criteria. Studies were rated for evidential consideration as high, intermediate, or low based upon the study design, number of participants, exposure measurement, and neurodevelopmental measures. All but one of the 27 studies evaluated showed some negative effects of pesticides on neurobehavioral development. A positive dose–response relationship between OP exposure and neurodevelopmental outcomes was found in all but one of the 12 studies that assessed dose–response. In the ten longitudinal studies that assessed prenatal exposure to OPs, cognitive deficits (related to working memory) were found in children at age 7 years, behavioral deficits (related to attention) seen mainly in toddlers, and motor deficits (abnormal reflexes) seen mainly in neonates. No meta-analysis was possible due to different measurements of exposure assessment and outcomes. Eleven studies (all longitudinal) were rated high, 14 studies were rated intermediate, and two studies were rated low. Evidence of neurological deficits associated with exposure to OP pesticides in children is growing. The studies reviewed collectively support the hypothesis that exposure to OP pesticides induces neurotoxic effects. Further research is needed to understand effects associated with exposure in critical windows

  6. Effects of methylmercury and alcohol exposure in Drosophila melanogaster: Potential risks in neurodevelopmental disorders.

    Science.gov (United States)

    Chauhan, Ved; Chauhan, Abha

    2016-06-01

    Extensive evidence suggests the role of oxidative stress in autism and other neurodevelopmental disorders. In this study, we investigated whether methylmercury (MeHg) and/or alcohol exposure has deleterious effects in Drosophila melanogaster (fruit flies). A diet containing different concentrations of MeHg in Drosophila induced free radical generation and increased lipid peroxidation (markers of oxidative stress) in a dose-dependent manner. This effect of MeHg on oxidative stress was enhanced by further exposure to alcohol. It was observed that alcohol alone could also induce free radical generation in flies. After alcohol exposure, MeHg did not affect the immobilization of flies, but it increased the recovery time in a concentration-dependent manner. MeHg significantly inhibited the activity of alcohol dehydrogenase (ADH) in a dose-dependent manner. Linear regression analysis showed a significant negative correlation between ADH activity and recovery time upon alcohol exposure in the flies fed a diet with MeHg. This relationship between ADH activity and recovery time after alcohol exposure was confirmed by adding 4-methyl pyrazole (an inhibitor of ADH) to the diet for the flies. These results suggest that consumption of alcohol by pregnant mothers who are exposed to MeHg may lead to increased oxidative stress and to increased length of time for alcohol clearance, which may have a direct impact on the development of the fetus, thereby increasing the risk of neurodevelopmental disorders. Published by Elsevier Ltd.

  7. The effect of kangaroo care on neurodevelopmental outcomes in preterm infants.

    Science.gov (United States)

    Head, Lauren M

    2014-01-01

    Preterm birth is associated with long-term deficits in executive functioning and cognitive performance. As advances in neonatal care enable more preterm infants to survive, development of strategies to address high rates of neurodevelopmental disabilities and poor academic achievement in preterm infants are crucial. Evidence suggests that infants' brains are plastic in nature and, therefore, can be shaped by the environment. Kangaroo care has become popularized as a means of modifying the stress of the NICU environment. However, few studies have examined whether kangaroo care affects neurodevelopmental outcomes in preterm infants. This review examined available literature that investigated the effect of kangaroo care on cognition in preterm infants. Current evidence suggests that short-term benefits of kangaroo care are associated with improved neurodevelopment. However, few studies have examined the long-term impact of kangaroo care on cognitive outcomes in preterm infants. To address neurological disparities in children born preterm, research using kangaroo care as a strategy to improve neurodevelopment in preterm infants is warranted.

  8. Effects of Cannabis on Neurocognitive Functioning: Recent Advances, Neurodevelopmental Influences, and Sex Differences

    Science.gov (United States)

    Crane, Natania A.; Schuster, Randi Melissa; Fusar-Poli, Paolo; Gonzalez, Raul

    2012-01-01

    Decades of research have examined the effects of cannabis on neurocognition. Recent advances in this field provide us with a better understanding of how cannabis use influences neurocognition both acutely (during intoxication) and non-acutely (after acute effects subside). Evidence of problems with episodic memory is one of the most consistent findings reported; however, several other neurocognitive domains appear to be adversely affected by cannabis use under various conditions. There is significant variability in findings across studies, thus a discussion of potential moderators is increasingly relevant. The purpose of this review was to 1) provide an update on research of cannabis’ acute and non-acute effects on neurocognition, with a focus on findings since 2007 and 2) suggest and discuss how neurodevelopmental issues and sex differences may influence cannabis effects on neurocognition. Finally we discuss how future investigations may lead to better understanding of the complex interplay among cannabis, stages of neurodevelopment, and sex on neurocognitive functioning. PMID:23129391

  9. Effect of co-twin gender on neurodevelopmental symptoms: a twin register study.

    Science.gov (United States)

    Eriksson, Jonna Maria; Lundström, Sebastian; Lichtenstein, Paul; Bejerot, Susanne; Eriksson, Elias

    2016-01-01

    Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders thought to have both genetic and environmental causes. It has been hypothesized that exposure to elevated levels of prenatal testosterone is associated with elevated traits of ASD and ADHD. Assuming that testosterone levels from a dizygotic male twin fetus may lead to enhanced testosterone exposure of its co-twins, we aimed to test the prenatal testosterone hypothesis by comparing same-sex with opposite-sex dizygotic twins with respect to neurodevelopmental symptoms. Neuropsychiatric traits were assessed in a population-based twin cohort from the Child and Adolescent Twin Study in Sweden (CATSS). Parental interviews were conducted for 16,312 dizygotic twins, 9 and 12 years old, with the Autism-Tics, ADHD, and other Comorbidities inventory (A-TAC). Girls with a female co-twin had an increased risk of reaching the cut-off score for ADHD compared with girls with a male co-twin. Both boys and girls with a female co-twin displayed a larger number of traits related to attention deficit and repetitive and stereotyped behaviors than those with a male twin. In girls, this also extended to social interaction and the combined measures for ASD and ADHD, however, with small effect sizes. Our results are reverse to what would have been expected from the prenatal testosterone hypothesis but consistent with a previous study of ASD and ADHD traits in dizygotic twins. The seemingly protective effect for girls of having a twin brother may be an effect of parent report bias, but may also be an unexpected effect of sharing the intrauterine environment with a male co-twin.

  10. The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs

    Directory of Open Access Journals (Sweden)

    Barrington Keith J

    2001-02-01

    Full Text Available Abstract Background Recent reports have raised concerns that postnatal steroids may cause neuro-developmental impairment in preterm infants. This systematic review was performed with the objective of determining whether glucocorticoid therapy, to prevent or treat bronchopulmonary dysplasia, impairs neuro-developmental outcomes in preterm infants. Method A systematic review of the literature was performed. Medline was searched and articles retrieved using predefined criteria. Data from randomized controlled trials with adequate neuro-developmental follow up (to at least one year were entered into a meta-analysis to determine the effects of postnatal treatment of preterm infants with glucocorticoids. Cerebral palsy rates, and neuro-developmental impairment (developmental score more than 2SD below the mean, or cerebral palsy or blindness were analyzed. The studies were divided into 2 groups according to the extent of contamination of the results by treatment of controls with steroids after the initial study period, those with less than 30% contamination, and those with more than 30% contamination or size of contamination not reported. Results Postnatal steroid therapy is associated with an increase in cerebral palsy and neuro-developmental impairment. The studies with less contamination show a greater effect of the steroids, consistent with a real direct toxic effect of steroids on the developing central nervous system. The typical relative risk for the development of cerebral palsy derived from studies with less than 30% contamination is 2.86 (95% CI 1.95, 4.19. The typical relative risk for the development of neuro-developmental disability among followed up infants from studies with less than 30% contamination is 1.66 (95% CI 1.26, 2.19. From this subgroup of studies, the number of premature infants who need to be treated to have one more infant with cerebral palsy (number needed to harm, NNH is 7; to have one more infant with neuro-developmental

  11. Effects of early nutrition and growth on brain volumes, white matter microstructure, and neurodevelopmental outcome in preterm newborns.

    Science.gov (United States)

    Coviello, Caterina; Keunen, Kristin; Kersbergen, Karina J; Groenendaal, Floris; Leemans, Alexander; Peels, Barbara; Isgum, Ivana; Viergever, Max A; de Vries, Linda S; Buonocore, Giuseppe; Carnielli, Virgilio P; Benders, Manon J N L

    2018-01-01

    BackgroundThis study aimed to investigate the effect of nutrition and growth during the first 4 weeks after birth on cerebral volumes and white matter maturation at term equivalent age (TEA) and on neurodevelopmental outcome at 2 years' corrected age (CA), in preterm infants.MethodsOne hundred thirty-one infants born at a gestational age (GA) brain development.

  12. [Effects of early neurodevelopmental treatment on motor and cognitive development of critically ill premature infants].

    Science.gov (United States)

    Li, Na; Kang, Lin-Min; Wang, Qiu; Yu, Tao; Ma, Dan; Luo, Rong

    2013-03-01

    To study the effects of neurodevelopmental treatment (NDT) on motor and cognitive development of critically ill premature infants. There were 203 infants, who were less than 32 week gestational age (GA), with very-low-birth weight, were included in the study. The infants were assigned to NDT group (n = 96) or control group (n = 107) according to the parent's decision. The infants in NDT group received NDT intervention once per week from corrected age (CA) 1 month to 3 months, and 3 to 5 times per week in the following 9 months. NDT intervention included elongation, establishing alignment, optimizing base of support, facilitation and inhibition, stimulation for activating muscle activity. Both groups received family intervention, such as massage and exercise based on early education. Bayley Scales of Infant Development-II (BSID-II) score was assessed at 3,6,9,12 months CA for all the infants. NDT intervention achieved significant effects on motor and cognitive development. Mental development index (MDI) and psychomotor development index (PDI) of BSID-II were significant higher in NDT group (P children in NDT group (16.67%) and 12 (12.12%) in control group at 12 months CA, there was no significant difference between the two groups (P > 0.05). NDT intervention can improve motor and cognitive development in critically ill premature infants within 12 months CA.

  13. Assisted reproduction and child neurodevelopmental outcomes

    DEFF Research Database (Denmark)

    Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler

    2013-01-01

    To systematically review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception.......To systematically review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception....

  14. Effect of neurodevelopmental treatment-based physical therapy on the change of muscle strength, spasticity, and gross motor function in children with spastic cerebral palsy

    National Research Council Canada - National Science Library

    Park, Eun-Young; Kim, Won-Ho

    2017-01-01

    [Purpose] This study aimed to investigate the effectiveness of neurodevelopmental treatment-based physical therapy on muscle tone, strength, and gross motor function in children with spastic cerebral palsy...

  15. The effect of musical attention control training (MACT) on attention skills of adolescents with neurodevelopmental delays: a pilot study.

    Science.gov (United States)

    Pasiali, Varvara; LaGasse, A Blythe; Penn, Saundra L

    2014-01-01

    Given the effect of musical training on the rate and accuracy of processing auditory information, therapeutic uses of music may potentially have remedial benefits for individuals with neurodevelopmental deficits. However, additional studies are needed to establish efficacy of music therapy interventions for attention skills in children/adolescents with neurodevelopmental disabilities including those with Autism Spectrum Disorders (ASD). To establish feasibility and preliminary efficacy of a group music therapy protocol to improve attention skills (sustained, selective, attentional control/switching) in adolescents diagnosed with autism and/or developmental delays. This single group pretest/posttest study took place in a private school for high functioning adolescents with neurodevelopmental delays. Nine students (4 males, 5 females), ages 13 to 20, participated in the study. Autism severity was assessed using the CARS2-HF and indicated the following distribution for study participants: severe (n = 3), mild (n = 4), or minimal/no (n = 2) symptoms. We assessed feasibility of implementing a 45-min Musical Attention Control Training (MACT) intervention delivered by a board-certified music therapist eight times over 6 weeks in a school setting. We also examined preliminary efficacy of the MACT to improve attention skills using the Test of Everyday Attention for Children (TEA-Ch). Parental consent rate was 100%. All nine participants successfully completed testing measures and 6 weeks of the intervention. Average participation rate was 97%. Data analysis showed positive trends and improvements on measures of attentional control/switching and selective attention. The results showed that the intervention and testing measures were feasible to implement and acceptable to the participants who all completed the protocol. Data analysis demonstrated positive trends indicating that more research on the use of music therapy attention training in high-functioning adolescents with

  16. Effectiveness of Neuro-Developmental Treatment (bobath concept) on postural control and balance in Cerebral Palsied Children.

    Science.gov (United States)

    Tekin, Fatih; Kavlak, Erdogan; Cavlak, Ugur; Altug, Filiz

    2017-11-17

    The aim of this study was to show the effects of an 8-week Neurodevelopmental Treatment based posture and balance training on postural control and balance in diparetic and hemiparetic Cerebral Palsied children (CPC). Fifteen CPC (aged 5-15 yrs) were recruited from Denizli Yağmur Çocukları Rehabilitation Centre. Gross Motor Function Classification System, Gross Motor Function Measure, 1-Min Walking Test, Modified Timed Up and Go Test, Paediatric Balance Scale, Functional Independence Measure for Children and Seated Postural Control Measure were used for assessment before and after treatment. An 8-week NDT based posture and balance training was applied to the CPC in one session (60-min) 2 days in a week. After the treatment program, all participants showed statistically significant improvements in terms of gross motor function (p< 0.05). They also showed statistically significant improvements about balance abilities and independence in terms of daily living activities (p< 0.05). Seated Postural Control Measure scores increased after the treatment program (p< 0.05). The results of this study indicate that an 8-week Neurodevelopmental Treatment based posture and balance training is an effective approach in order to improve functional motor level and functional independency by improving postural control and balance in diparetic and hemiparetic CPC.

  17. Risk and benefit assessment of potential neurodevelopmental effect resulting from consumption of marine fish from a coastal archipelago in China.

    Science.gov (United States)

    Gao, Yi-Xiong; Zhang, Hongxia; Yu, Xinwei; He, Jia-lu; Shang, Xiaohong; Li, Xiaowei; Zhao, Yunfeng; Wu, Yongning

    2014-06-04

    The aim of this study was to assess net neurodevelopmental effect via maternal consumption of marine fish. A total of thirty-one species were collected from Zhoushan, China. The net IQ point gain was assessed by FAO/WHO deterministic approach and probabilistic computation (if necessary). Results of the deterministic assessment of two samples belonging to Scoliodon sorrakowah showed negative IQ point gain in both common and extreme consumption scenarios (175 and 450 g/week, respectively); the net IQ gain caused by both consumption scenarios of other species were positive. Both consumption scenarios of Scoliodon sorrakowah showed beneficial neurodevelopmental effect according to probabilistic computation (95% CI for mean of net IQ gain: 0.0536-0.0554 and 0.1377-0.1425, respectively). Except for Scoliodon sorrakowah, this study indicates that both consumption scenarios of other studied species would be recommended according to the FAO/WHO approach. There would be no recommendation of consumption scenarios of Scoliodon sorrakowah for the reason for carefulness.

  18. Does the Kuleshov Effect really Exist?

    DEFF Research Database (Denmark)

    Barratt, Daniel; Cabak Rédei, Anna

    2013-01-01

    , sadness, and hunger/neutral conditions with equivalent stimuli. For each film sequence, the participant was asked: to rate the valence of the depicted person’s emotion; to rate how aroused the person appeared to be; and to identify the type of emotion that the person was feeling. The participant’s eye...... movements were recorded throughout the experiment using a remote eye-tracker (SMI iView X RED). A preliminary analysis of the results suggests that some sort of Kuleshov effect does in fact exist. For the different emotional conditions, the participants tended to choose the appropriate emotion more...

  19. Does the Kuleshov Effect Really Exist?

    DEFF Research Database (Denmark)

    Barratt, Daniel; Rédei, Anna Cabak; Innes-Ker, Åse

    2016-01-01

    to replicate Kuleshov’s original experiment using an improved experimental design. In a behavioral and eye tracking study, 36 participants were each presented with 24 film sequences of neutral faces across six emotional conditions. For each film sequence, the participants were asked to evaluate the emotion...... of the target person in terms of valence, arousal, and category. The participants’ eye movements were recorded throughout. The results suggest that some sort of Kuleshov effect does in fact exist. For each emotional condition, the participants tended to choose the appropriate category more frequently than...... between the emotional conditions....

  20. ACE: Health - Neurodevelopmental Disorders

    Science.gov (United States)

    Information about children reported to have ever been diagnosed with four different neurodevelopmental disorders: attention-deficit/hyperactivity disorder (ADHD), learning disabilities, autism, and intellectual disability.

  1. Neurodevelopmental hypothesis of schizophrenia

    National Research Council Canada - National Science Library

    Owen, Michael J; O'Donovan, Michael C; Thapar, Anita; Craddock, Nicholas

    2011-01-01

    The neurodevelopmental hypothesis of schizophrenia provided a valuable framework that allowed a condition that usually presents with frank disorder in adolescence or early adulthood to be understood...

  2. Children with neurodevelopmental disorders: The burden and psychological effects on caregivers in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Andrew T Olagunju

    2017-01-01

    Full Text Available Background: Children with neurodevelopmental disorders (CNDs are a group requiring more attention as their care is often challenging, particularly for parents with primary caregiving roles in resource-restricted settings. This study had set out to investigate the burden and psychological distress among caregivers of children with neurodevelopmental delays. Materials and Methods: A total of 68 caregivers were recruited during the 2013 annual autism health program organized by the College of Medicine, University of Lagos in collaboration with Guaranty Trust Bank, Nigeria and Blazing Trails, USA. Of these caregivers, 60 respondents (caregivers and children were included in the final analyses due to poorly completed questionnaires. The Zarit Caregivers Burden Scale (ZCBS and General Health Questionnaire version 12 (GHQ-12 were administered to elicit caregivers' experience with respect to burden and psychological distress, respectively. Results: Of the 60 participants included in the final analyses, the majority constituted parents (96.3% with mothers accounting for 71.7%; 28 (46.7% participants were government workers and 3 (5% were full-time housewives. The mean age of CNDs was 6.8 (±3.2 years, and 33 (55.0% were males. Delivery by cesarian section was reported in 19 (31.8%. The common presenting complaints by caregivers were inability to walk (32.7%, repetitive behavior (25.5%, difficulty with verbal communication (10.9%, nonsocialization (9.1%, seizures (9.1%, and hyperactivity (3.6%. Problems were noticed at ≤ 1 year in 46.7% while they were noticed after 2 years in more than half the children, and a little above one-eighth (14% had siblings with similar problems. On the ZCBS, nine (15.0% caregivers reported a significant burden. In addition, 23 (38.3% caregivers had psychological distress. Caregivers' burden was significantly related to the report of psychological distress in caregivers (P < 0.001 and there was a trend toward the presence of

  3. Differential effects of rhythmic auditory stimulation and neurodevelopmental treatment/Bobath on gait patterns in adults with cerebral palsy: a randomized controlled trial.

    Science.gov (United States)

    Kim, Soo Ji; Kwak, Eunmi E; Park, Eun Sook; Cho, Sung-Rae

    2012-10-01

    To investigate the effects of rhythmic auditory stimulation (RAS) on gait patterns in comparison with changes after neurodevelopmental treatment (NDT/Bobath) in adults with cerebral palsy. A repeated-measures analysis between the pretreatment and posttreatment tests and a comparison study between groups. Human gait analysis laboratory. Twenty-eight cerebral palsy patients with bilateral spasticity participated in this study. The subjects were randomly allocated to either neurodevelopmental treatment (n = 13) or rhythmic auditory stimulation (n = 15). Gait training with rhythmic auditory stimulation or neurodevelopmental treatment was performed three sessions per week for three weeks. Temporal and kinematic data were analysed before and after the intervention. Rhythmic auditory stimulation was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard, while neurodevelopmental treatment was implemented following the traditional method. Temporal data, kinematic parameters and gait deviation index as a measure of overall gait pathology were assessed. Temporal gait measures revealed that rhythmic auditory stimulation significantly increased cadence, walking velocity, stride length, and step length (P < 0.05). Kinematic data demonstrated that anterior tilt of the pelvis and hip flexion during a gait cycle was significantly ameliorated after rhythmic auditory stimulation (P < 0.05). Gait deviation index also showed modest improvement in cerebral palsy patients treated with rhythmic auditory stimulation (P < 0.05). However, neurodevelopmental treatment showed that internal and external rotations of hip joints were significantly improved, whereas rhythmic auditory stimulation showed aggravated maximal internal rotation in the transverse plane (P < 0.05). Gait training with rhythmic auditory stimulation or neurodevelopmental treatment elicited differential effects on gait patterns in adults with cerebral palsy.

  4. A three-center, randomized, controlled trial of individualized developmental care for very low birth weight preterm infants: medical, neurodevelopmental, parenting, and caregiving effects.

    NARCIS (Netherlands)

    Als, H.; Gilkerson, L.; Duffy, F.H.; McAnulty, G.B.; Buehler, D.M.; Berg, K. van den; Sweet, N.; Sell, E.; Parad, R.B.; Ringer, S.A.; Butler, S.C.; Blickman, J.G.; Jones, K.J.

    2004-01-01

    Medical, neurodevelopmental, and parenting effects of individualized developmental care were investigated in a three-center, randomized, controlled trial. A total of 92 preterm infants, weighing less than 1250 g and aged less than 28 weeks, participated. Outcome measures included medical,

  5. Effectiveness of Existing International Nuclear Liability Regime

    Energy Technology Data Exchange (ETDEWEB)

    Al-Doais, Salwa; Kessel, Daivd [KEPCO International Nuclear Graduate School, Daejeon (Korea, Republic of)

    2015-10-15

    The first convention was the Paris Convention on Third Party Liability in the Field of Nuclear Energy (the Paris Convention) had been adopted on 29 July 1960 under the auspices of the OECD, and entered into force on 1 April 1968. In 1963,the Brussels Convention - supplementary to the Paris Convention- was adopted in to provide additional funds to compensate damage as a result of a nuclear incident where Paris Convention funds proved to be insufficient. The IAEA's first convention was the Vienna Convention on Civil Liability for Nuclear Damage (the Vienna Convention) which adopted on 21 May 1963,and entered into force in 1977. Both the Paris Convention and the Vienna Convention laid down very similar nuclear liability rules based on the same general principles. The broad principles in these conventions can be summarized as follows: 1- The no-fault liability principle (strict liability) 2- Liability is channeled exclusively to the operator of the nuclear installation (legal channeling) 3- Only courts of the state in which the nuclear accident occurs would have jurisdiction (exclusive jurisdiction) 4- Limitation of the amount of liability and the time frame for claiming damages (limited liability) 5- The operator is required to have adequate insurance or financial guarantees to the extent of its liability amount (liability must be financially secured). 6- Liability is limited in time. Compensation rights are extinguished after specific time. 7- Non-discrimination of victims on the grounds of nationality, domicile or residence. Nuclear liability conventions objective is to provide adequate compensation payments to victims of a nuclear accident. Procedures for receiving these compensation are controlled by some rules such as exclusive jurisdiction, that rule need a further amendment to ensure the effectiveness of the exiting nuclear liability regime . Membership of the Conventions is a critical issue, because the existence of the conventions without being party to

  6. Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system

    Directory of Open Access Journals (Sweden)

    Ruthazer Edward S

    2010-01-01

    Full Text Available Abstract Background Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the Xenopus laevis tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits. Results Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL-1β, IL-6 and tumor necrosis factor (TNF-α. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-α on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-α resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-α treatment also enhanced the

  7. Effects of Johnstone pressure splints combined with neurodevelopmental therapy on spasticity and cutaneous sensory inputs in spastic cerebral palsy.

    Science.gov (United States)

    Kerem, M; Livanelioglu, A; Topcu, M

    2001-05-01

    The purpose of this study was to investigate the effectiveness of Johnstone pressure splints (JPSs) on spasticity and cutaneous sensory inputs in children with spastic cerebral palsy (CP). Thirty-four children with spastic diplegic CP participated in this study. Children whose motor development levels were similar were divided into a treatment and a control group. Each group consisted of 17 participants (six females and 11 males). Mean age of the treatment group was 48.82 months (SEM 4.42), and the control group, 47.52 months (SEM 5.27). The treatment group underwent Bobath's neurodevelopmental therapy (NDT) combined with JPSs. The control group underwent NDT alone five days a week for three months. Before and after treatments, lower-extremity passive range of motion (ROM) by goniometric measurements, spasticity by Modified Ashworth Scale (MAS), and somatosensory evoked potentials (SEPs) were measured. Passive ROM showed significant improvements in both groups (p<0.01). In the treatment group, all MAS scores increased. In the control group, the difference was significant except for values of internal rotator muscles. Improvements in passive ROM in the treatment group were significantly higher than the control group except in hip abduction and external rotation (p<0.05). MAS scores of the treatment group were significantly higher than the control group (p<0.05). SEP values increased in both groups but values of the treatment group were significantly higher than the control group (p<0.05).

  8. Assessing the independent and joint effects of un-medicated prenatal depressive symptoms and alcohol consumption in pregnancy and infant neurodevelopmental outcomes

    Science.gov (United States)

    Bandoli, G; Coles, CD; Kable, JA; Wertelecki, W; Granovska, IV; Pashtepa, AO; Chambers, CD

    2016-01-01

    Background Prenatal alcohol exposure (PAE) is an established risk factor for neurodevelopmental deficits in the offspring. Prenatal depression has been associated with neurodevelopmental deficits in the offspring, although investigations into un-medicated prenatal depression have been inconsistent. We hypothesized that un-medicated prenatal depressive symptoms would independently and jointly with PAE predict neurodevelopmental outcomes in infant offspring. Methods We studied 344 participants from a randomized clinical trial of multivitamin supplements in pregnant women in Ukraine. Women were recruited based upon peri-conceptional alcohol use and followed up to 12 months postpartum. Prenatal depressive symptoms were assessed at approximately 32 weeks of gestation using the Beck Depression Scale. Neurodevelopment was assessed with the Bayley Scales for Infant Development II Mental Development Index (MDI) and Psychomotor Development Index (PDI) at 6 and 12 months postpartum. Generalized linear regression models were constructed to assess the independent and joint effects of prenatal depressive symptoms and PAE in models adjusted for sociodemographic and pregnancy characteristics. Results PAE was independently associated with deficits in neurodevelopmental outcomes at 6 and 12 months, however, level of prenatal depressive symptoms was not. We found marginal evidence of synergism of depressive symptoms and PAE, with larger deficits in those with both exposures observed for the PDI-6 months (p=0.05) and MDI-12 months (p=0.09). Additionally, there was a suggestion of sexual dimorphism; females had stronger deficits from joint exposures than males (depressive symptom (MDI-6 months) female: −8.28, 95% CI −13.06, −3.49; male: 0.68, 95% CI −4.58, 5.94; p for interaction 0.04). While not statistically significant for the MDI or PDI at 12 months, the trend persisted. Conclusion Infants exposed to PAE and prenatal depression may be at an increased risk of

  9. The Effects of Live Music as the Discriminative Stimulus and Reinforcer on the Skill Acquisition of Learners with Neurodevelopmental Disorders

    Science.gov (United States)

    Harms, Melanie D.

    2013-01-01

    Individuals with neurodevelopmental disorders are challenged with memory and language deficits that impact their skills acquisition (Martin, Klusek, Estigarriba, & Roberts, 2009; Turner & Alborz, 2003). The value of music when applied as an antecedent and a reinforcer has long been established to address such memory and language deficits…

  10. Behavioral effects of the benzodiazepine-positive allosteric modulator SH-053-2'F-S-CH₃ in an immune-mediated neurodevelopmental disruption model.

    Science.gov (United States)

    Richetto, Juliet; Labouesse, Marie A; Poe, Michael M; Cook, James M; Grace, Anthony A; Riva, Marco A; Meyer, Urs

    2015-01-30

    Impaired γ-aminobutyric acid (GABA) signaling may contribute to the emergence of cognitive deficits and subcortical dopaminergic hyperactivity in patients with schizophrenia and related psychotic disorders. Against this background, it has been proposed that pharmacological interventions targeting GABAergic dysfunctions may prove useful in correcting such cognitive impairments and dopaminergic imbalances. Here, we explored possible beneficial effects of the benzodiazepine-positive allosteric modulator SH-053-2'F-S-CH₃, with partial selectivity at the α2, α3, and α5 subunits of the GABAA receptor in an immune-mediated neurodevelopmental disruption model. The model is based on prenatal administration of the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)] in mice, which is known to capture various GABAergic, dopamine-related, and cognitive abnormalities implicated in schizophrenia and related disorders. Real-time polymerase chain reaction analyses confirmed the expected alterations in GABAA receptor α subunit gene expression in the medial prefrontal cortices and ventral hippocampi of adult poly(I:C) offspring relative to control offspring. Systemic administration of SH-053-2'F-S-CH₃ failed to normalize the poly(I:C)-induced deficits in working memory and social interaction, but instead impaired performance in these cognitive and behavioral domains both in control and poly(I:C) offspring. In contrast, SH-053-2'F-S-CH₃ was highly effective in mitigating the poly(I:C)-induced amphetamine hypersensitivity phenotype without causing side effects in control offspring. Our preclinical data suggest that benzodiazepine-like positive allosteric modulators with activity at the α2, α3, and α5 subunits of the GABAA receptor may be particularly useful in correcting pathological overactivity of the dopaminergic system, but they may be ineffective in targeting multiple pathological domains that involve the co-existence of psychotic, social, and cognitive

  11. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    Energy Technology Data Exchange (ETDEWEB)

    Theunissen, P.T., E-mail: Peter.Theunissen@rivm.nl [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Robinson, J.F. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Pennings, J.L.A. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Herwijnen, M.H. van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Kleinjans, J.C.S. [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Piersma, A.H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Institute for Risk Assessment Sciences, Faculty of Veterinary Sciences, Utrecht University, Utrecht (Netherlands)

    2012-08-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  12. Neurodevelopmental effects of maternal nutritional status and exposure to methylmercury from eating fish during pregnancy.

    Science.gov (United States)

    Davidson, Philip W; Strain, J J; Myers, Gary J; Thurston, Sally W; Bonham, Maxine P; Shamlaye, Conrad F; Stokes-Riner, Abbie; Wallace, Julie M W; Robson, Paula J; Duffy, Emeir M; Georger, Lesley A; Sloane-Reeves, Jean; Cernichiari, Elsa; Canfield, Richard L; Cox, Christopher; Huang, Li Shan; Janciuras, Joanne; Clarkson, Thomas W

    2008-09-01

    Fish contain nutrients that promote optimal brain growth and development but also contain methylmercury (MeHg) that can have toxic effects. The present study tested the hypothesis that the intake of selected nutrients in fish or measures of maternal nutritional status may represent important confounders when estimating the effects of prenatal methylmercury exposure on child development. The study took place in the Republic of Seychelles, an Indian Ocean archipelago where fish consumption is high. A longitudinal cohort study design was used. A total of 300 mothers were enrolled early in pregnancy. Nutrients considered to be important for brain development were measured during pregnancy along with prenatal MeHg exposure. The children were evaluated periodically to age 30 months. There were 229 children with complete outcome and covariate data for analysis. The primary endpoint was the Bayley Scales of Infant Development-II (BSID-II), administered at 9 and 30 months of age. Combinations of four secondary measures of infant cognition and memory were also given at 5, 9 and 25 months. Cohort mothers consumed an average of 537 g of fish (nine meals containing fish) per week. The average prenatal MeHg exposure was 5.9 ppm in maternal hair. The primary analysis examined the associations between MeHg, maternal nutritional measures and children's scores on the BSID-II and showed an adverse association between MeHg and the mean Psychomotor Developmental Index (PDI) score at 30 months. Secondary analyses of the association between the PDI and only MeHg alone or nutritional factors alone showed only a borderline significant association between MeHg and the PDI at 30 months and no associations with nutritional factors. One experimental measure at 5 months of age was positively associated with iodine status, but not prenatal MeHg exposure. These findings suggest a possible confounding role of maternal nutrition in studies examining associations between prenatal MeHg exposures and

  13. Pediatric Neurodevelopmental Treatment

    Science.gov (United States)

    Camacho, Ricardo; McCauley, Brandon; Szczech Moser, Christy

    2016-01-01

    Over 70 years ago Dr. Karel Bobath and his wife Bertha Bobath began to craft the therapeutic intervention now known as neurodevelopmental treatment (NDT). This edition of Reviews, Tools, and Resources will highlight a historical review of research studies that have been completed, current websites, books, and blogs focusing on NDT.

  14. Sleep in Neurodevelopmental Disorders

    Science.gov (United States)

    Esbensen, Anna J; Schwichtenberg, Amy J

    2017-01-01

    Individuals with intellectual and developmental disabilities (IDD) experience sleep problems at higher rates than the general population. Although individuals with IDD are a heterogeneous group, several sleep problems cluster within genetic syndromes or disorders. This review summarizes the prevalence of sleep problems experienced by individuals with Angelman syndrome, Cornelia de Lange syndrome, Cri du Chat syndrome, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, Williams syndrome, autism spectrum disorder, and idiopathic IDD. Factors associated with sleep problems and the evidence for sleep treatments are reviewed for each neurodevelopmental disorder. Sleep research advancements in neurodevelopmental disorders are reviewed, including the need for consistency in defining and measuring sleep problems, considerations for research design and reporting of results, and considerations when evaluating sleep treatments. PMID:28503406

  15. Neurodevelopmental and neurobehavioural effects of polybrominated and perfluorinated chemicals: a systematic review of the epidemiological literature using a quality assessment scheme.

    Science.gov (United States)

    Roth, N; Wilks, M F

    2014-10-15

    Concerns over effects of halogenated persistent environmental contaminants on the developing brain have been expressed for many years, and human biomonitoring has confirmed that low-level, prenatal and/or postnatal exposure of children to these chemicals is ubiquitous. Over the last decade there have been increasing reports in the epidemiological literature of the potential association of exposure to polybromo diphenylethers (PBDEs) and perfluorinated chemicals (PFCs) with neurodevelopmental and/or neurobehavioural effects in infants and children, such as adverse birth outcomes, cognitive deficits, developmental delay and attention deficit hyperactivity disorders (ADHD). However, direct evidence from epidemiology studies has been limited and contradictory. Given the general lack of comparability across studies in terms of design, conduct, methodology and reporting, we developed a checklist-type quality assessment scheme based on the STROBE guidelines and the proposed HONEES criteria, and conducted a systematic review of the epidemiological peer-reviewed literature published since 2006 on neurodevelopmental and/or neurobehavioural effects following prenatal and postnatal exposure to PBDEs and PFCs. We rated 7 of the 18 studies that met our inclusion criteria as being of high quality, 7 of moderate quality and 4 of low quality. Frequently observed shortcomings were the lack of consideration of confounding factors; uncertainties regarding exposure characterization; inadequate sample size; the lack of a clear dose-response; and the representativeness/generalizability of the results. Collectively, the epidemiological evidence does currently not support a strong causal association between PBDEs and PFCs and adverse neurodevelopmental and neurobehavioural outcomes in infants and children. However, despite their limitations, the studies raise questions that require further investigation through hypothesis-driven studies using more harmonized study designs and methodologies

  16. Epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders.

    Science.gov (United States)

    Weber-Stadlbauer, U

    2017-05-02

    Prenatal infection is an environmental risk factor for various brain disorders with neurodevelopmental components, including autism spectrum disorder and schizophrenia. Modeling this association in animals shows that maternal immune activation negatively affects fetal brain development and leads to the emergence of behavioral disturbances later in life. Recent discoveries in these preclinical models suggest that epigenetic modifications may be a critical molecular mechanism by which prenatal immune activation can mediate changes in brain development and functions, even across generations. This review discusses the potential epigenetic mechanisms underlying the effects of prenatal infections, thereby highlighting how infection-mediated epigenetic reprogramming may contribute to the transgenerational transmission of pathological traits. The identification of epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders appears relevant to brain disorders independently of existing diagnostic classifications and may help identifying complex patterns of transgenerational disease transmission beyond genetic inheritance. The consideration of ancestral infectious histories may be of great clinical interest and may be pivotal for developing new preventive treatment strategies against infection-mediated neurodevelopmental disorders.

  17. 42 CFR 137.3 - Effect on existing Tribal rights.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Effect on existing Tribal rights. 137.3 Section 137.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE General Provisions § 137.3 Effect on existing...

  18. PURA-related neurodevelopmental disorders

    OpenAIRE

    Reijnders, Margot R F; Leventer, Richard J; Lee, Boo Hon; Baralle, Diana; Selber, Paulo; Paciorkowski, Alex R; Hunt, David

    2017-01-01

    Clinical characteristics. PURA-related neurodevelopmental disorders include PURA syndrome, caused by a heterozygous pathogenic sequence variant in PURA, and 5q31.3 deletion syndrome, caused by a genomic 5q31.3 deletion encompassing all or part of PURA. PURA-related neurodevelopmental disorders are characterized by moderate to severe neurodevelopmental delay with absence of speech in most and lack of independent ambulation in many. Early-onset problems can include hypotonia, hypothermia, hyper...

  19. Reversing Neurodevelopmental Disorders in Adults

    National Research Council Canada - National Science Library

    Ehninger, Dan; Li, Weidong; Fox, Kevin; Stryker, Michael P; Silva, Alcino J

    2008-01-01

    .... Surprisingly, a number of recent animal model studies of neurodevelopmental disorders demonstrate that reversing the underlying molecular deficits can result in substantial improvements in function...

  20. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Amin Mottahedin

    2017-07-01

    Full Text Available The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function. In this article, we will review the role of glia cells in synaptic physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following perinatal inflammatory challenges and potential implications for neurodevelopmental and neurodegenerative disorders.

  1. Neurodevelopmental treatment after stroke : a comparative study

    NARCIS (Netherlands)

    Dr. T.B. Hafsteinsdóttir; A Algra; M.H.F. Grypdonck; L.J. Kappelle

    2005-01-01

    Background: Neurodevelopmental treatment (NDT) is a rehabilitation approach increasingly used in the care of stroke patients, although no evidence has been provided for its efficacy. Objective: To investigate the effects of NDT on the functional status and quality of life (QoL) of patients

  2. Lifestyle during pregnancy: neurodevelopmental effects at 5 years of age. The design and implementation of a prospective follow-up study

    DEFF Research Database (Denmark)

    Kesmodel, Ulrik Schiøler; Underbjerg, Mette; Kilburn, Tina Røndrup

    2010-01-01

    BACKGROUND: It has been suggested that even mild exposure to alcohol, caffeine, smoking, and poor diet may have adverse long-term neurodevelopmental effects. In addition, there is evidence that timing of high exposures (e.g. binge drinking) can have particularly negative effects. This paper...... describes the design and implementation of The Lifestyle During Pregnancy Study addressing major methodological challenges for studies in this field. The study examines the effects of lifestyle during pregnancy on offspring neurodevelopment. METHODS: In 2003, we initiated a prospective follow-up of 1750...... alcohol drinking patterns before and during pregnancy, caffeine intake, smoking, diet, and other lifestyle, medical, and sociodemographic factors. RESULTS: At the age of 5 years, the children and their mothers participated in a comprehensive assessment of neurobehavioural development focusing on global...

  3. A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.

    Directory of Open Access Journals (Sweden)

    Swati Khare

    Full Text Available The autosomal dominant spinocerebellar ataxias (SCAs are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3. We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR. Together, these results indicate that the neurodevelopmental

  4. A KCNC3 mutation causes a neurodevelopmental, non-progressive SCA13 subtype associated with dominant negative effects and aberrant EGFR trafficking.

    Science.gov (United States)

    Khare, Swati; Nick, Jerelyn A; Zhang, Yalan; Galeano, Kira; Butler, Brittany; Khoshbouei, Habibeh; Rayaprolu, Sruti; Hathorn, Tyisha; Ranum, Laura P W; Smithson, Lisa; Golde, Todd E; Paucar, Martin; Morse, Richard; Raff, Michael; Simon, Julie; Nordenskjöld, Magnus; Wirdefeldt, Karin; Rincon-Limas, Diego E; Lewis, Jada; Kaczmarek, Leonard K; Fernandez-Funez, Pedro; Nick, Harry S; Waters, Michael F

    2017-01-01

    The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3). We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT) protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr) results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR). Together, these results indicate that the neurodevelopmental consequences of

  5. Treatments for Neurodevelopmental Disorders

    DEFF Research Database (Denmark)

    Di Pietro, Nina C; Whiteley, Louise Emma; Mizgalewicz, Ania

    2013-01-01

    The Internet is a major source of health-related information for parents of sick children despite concerns surrounding quality. For neurodevelopmental disorders, the websites of advocacy groups are a largely unexamined source of information. We evaluated treatment information posted on nine highly......-trafficked advocacy websites for autism, cerebral palsy, and fetal alcohol spectrum disorder. We found that the majority of claims about treatment safety and efficacy were unsubstantiated. Instead, a range of rhetorical strategies were used to imply scientific support. When peer-reviewed publications were cited, 20...... % were incorrect or irrelevant. We call for new partnerships between advocacy and experts in developmental disorders to ensure better accuracy and higher transparency about how treatment information is selected and evidenced on advocacy websites....

  6. Neurodevelopmental correlates in schizophrenia

    Directory of Open Access Journals (Sweden)

    Ivković Maja

    2003-01-01

    Full Text Available Contemporary aetiopathogenetic considerations, based on neuro-imaging genetic and developmental neurobiology studies, suggest neurodevelopmental origin of schizophrenia. Several lines of evidence including structural abnormalities on in vivo brain imaging, the excess of prenatal and obstetric complications and the association of congenital and minor physical anomalies with schizophrenia, strongly indicate the neurodevelopmental pathogenesis of schizophrenia. On the other hand, controversial concept of psychotic continuum suggests schizophrenia and depression sharing the same genetic contribution to the pathogenesis. If this would be the case, depression could also be considered as neuro developmental disorder. The aims of the study were to investigate the association between: a pregnancy and birth complications (PBC, and b minor physical anomalies (MPA and schizophrenia or depression. Experimental groups consisted of 60 schizophrenic, 28 major depression patients and 30 healthy controls. All patients were diagnosed according to DSM-IV. Schizophrenic group was divided with regard to PANSS score into positive (n=32 and negative form (n=28 subgroups. PBC information were gathered from maternal recall while MPA were examined by using Waldrop scale for adults. The results showed that negative and positive schizophrenic subgroups had significantly more PBC than depressive group (p<0,05, as well than controls (p<0,001; p<0,05; respectively. There was no significant trend for more PBC in negative than in positive subgroup. All schizophrenic patients had higher rates of MPA than depressives (p<0,05. This trend for more MPA was not significant in comparison with healthy controls. These findings suggest that schizophrenia, especially its negative forms, could be considered as a member of the spectrum of neuro developmental disorders, which does not seem to be the case with depression. PBC and MPA could also be valuable in evaluation of risks for

  7. Prospective study of the effect of sensory integration, neurodevelopmental treatment, and perceptual-motor therapy on the sensorimotor performance in children with mild mental retardation.

    Science.gov (United States)

    Wuang, Yee-Pay; Wang, Chih-Chung; Huang, Mao-Hsiung; Su, Chwen-Yng

    2009-01-01

    This quasi-experimental study compared the effect of sensory integrative (SI) therapy, neurodevelopmental treatment (NDT), and perceptual-motor (PM) approach on children with mild mental retardation. Children (N = 120) were randomly assigned to intervention with SI, NDT, or PM; another 40 children served as control participants. All children were assessed with measures of sensorimotor function. After intervention, the treatment groups significantly outperformed the control group on almost all measures. The SI group demonstrated a greater pretest-posttest change on fine motor, upper-limb coordination, and SI functioning. The PM group showed significant gains in gross motor skills, whereas the NDT group had the smallest change in most measures. SI, NDT, and PM improved sensorimotor function among children with mild mental retardation. The choice of sensorimotor approaches should be determined on the basis of the child's particular needs because each approach may have an advantage in certain aspects of sensorimotor function.

  8. 42 CFR 136.118 - Effect on existing rights.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Effect on existing rights. 136.118 Section 136.118 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES INDIAN HEALTH Grants for Development, Construction, and Operation of...

  9. Emerging pharmacotherapies for neurodevelopmental disorders.

    Science.gov (United States)

    Wetmore, Daniel Z; Garner, Craig C

    2010-09-01

    A growing and interdisciplinary translational neuroscience research effort for neurodevelopmental disorders (NDDs) is investigating the mechanisms of dysfunction and testing effective treatment strategies in animal models and, when possible, in the clinic. NDDs with a genetic basis have received particular attention. Transgenic animals that mimic genetic insults responsible for disease in man have provided insight about mechanisms of dysfunction, and, surprisingly, have shown that cognitive deficits can be addressed in adult animals. This review will present recent translational research based on animal models of genetic NDDs, as well as pharmacotherapeutic strategies under development to address deficits of brain function for Down syndrome, fragile X syndrome, Rett syndrome, neurofibromatosis-1, tuberous sclerosis, and autism. Although these disorders vary in underlying causes and clinical presentation, common pathways and mechanisms for dysfunction have been observed. These include abnormal gene dosage, imbalance among neurotransmitter systems, and deficits in the development, maintenance and plasticity of neuronal circuits. NDDs affect multiple brain systems and behaviors that may be amenable to drug therapies that target distinct deficits. A primary goal of translational research is to replace symptomatic and supportive drug therapies with pharmacotherapies based on a principled understanding of the causes of dysfunction. Based on this principle, several recently developed therapeutic strategies offer clear promise for clinical development in man.

  10. Is there a relationship between the rise in thyroid and neurodevelopmental health effects in North America and the rise in concentrations of PBDEs in the environment? An update

    Energy Technology Data Exchange (ETDEWEB)

    Muir, T. [Environment Canada, Burlington, ON (Canada)

    2004-09-15

    In a previous paper on this question, data on an apparently rising prevalence of hypothyroidism, and neurodevelopmental deficits in children was presented. In this context, the issue of the potential for the observed, exponentially increasing levels of PBDEs in the environment to contribute to this expressed clinical burden of disease was raised. This potential contribution was raised because of evidence that the toxicological endpoints of concern for PBDEs include thyroid hormone disruption and neurodevelopmental deficits, and are similar to those seen earlier for PCBs, and DDT. As well, structural and toxicological similarities to PBBs, PCDDs, PCDFs are also part of the concern. Also raised as issues for further research were two things. First, there is a need in risk assessment to move beyond the focus on the average or median body burden, tissue or human milk concentrations, to account for the population distribution of the concentrations, and the percentiles in the tails of the distribution, particularly the high exposure portion. Second, interactions and additive exposures to and effects of the above mentioned, and other compounds or substances, (e.g. perchlorate, mercury, lead) need to be considered when talking about the ''safety'' of individual compounds. The aim of this paper is to examine - using Monte Carlo methods applied to the reported human milk (lipid weight) concentrations - the probability distributions, and the population percentiles, of the times required for PBDEs to reach a critical value of 1250 ng/g found by the Jacobsons, for PCBs, to be associated with learning impairments, intellectual deficits, and IQ loss in the offspring. In addition, historical body burdens of PCBs and DDT will be taken from the literature, and using estimates derived here of the distribution of the 2002 human milk levels of these compounds, the times required for PBDEs, plus PCBs and DDT, to reach 1250 ng/g will be simulated. Finally, note will

  11. Lifestyle during pregnancy: neurodevelopmental effects at 5 years of age. The design and implementation of a prospective follow-up study.

    Science.gov (United States)

    Kesmodel, Ulrik Schiøler; Underbjerg, Mette; Kilburn, Tina Røndrup; Bakketeig, Leiv; Mortensen, Erik Lykke; Landrø, Nils Inge; Schendel, Diana; Bertrand, Jacquelyn; Grove, Jakob; Ebrahim, Shahul; Thorsen, Poul

    2010-03-01

    It has been suggested that even mild exposure to alcohol, caffeine, smoking, and poor diet may have adverse long-term neurodevelopmental effects. In addition, there is evidence that timing of high exposures (e.g. binge drinking) can have particularly negative effects. This paper describes the design and implementation of The Lifestyle During Pregnancy Study addressing major methodological challenges for studies in this field. The study examines the effects of lifestyle during pregnancy on offspring neurodevelopment. In 2003, we initiated a prospective follow-up of 1750 mother-child pairs, sampled on the basis of maternal alcohol drinking patterns from The Danish National Birth Cohort (DNBC), a study of 101,042 pregnancies enrolled 1997-2003. Data collection in the DNBC involved four prenatal and postnatal maternal interviews, providing detailed information on maternal alcohol drinking patterns before and during pregnancy, caffeine intake, smoking, diet, and other lifestyle, medical, and sociodemographic factors. At the age of 5 years, the children and their mothers participated in a comprehensive assessment of neurobehavioural development focusing on global cognition, specific cognitive functions, and behaviour. Two new tests assessing attention and speed of information processing among children were developed, and data on important potential confounders such as maternal intelligence quotient, vision, and hearing abilities were collected. Efforts were made to standardise procedures and obtain high inter-rater reliability. We expect that the study will illuminate the significance or lack of significance of maternal lifestyle during pregnancy and contribute to better understanding the effects of alcohol drinking during pregnancy at low to moderate consumption levels.

  12. Drug development for neurodevelopmental disorders

    DEFF Research Database (Denmark)

    Berry-Kravis, Elizabeth M; Lindemann, Lothar; Jønch, Aia E

    2018-01-01

    Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal gene...

  13. Knowledge of neurodevelopmental profile as one of the XXI century manager’s basic competences

    Directory of Open Access Journals (Sweden)

    Agnieszka Kowalczyk-Kassyk

    2011-01-01

    Full Text Available Majority of situations which man participates in are social situations, which other people attend directly or indirectly. Members of a group are connected with each other by mutual relationships system, which come into existence and change via continuous mutual influencing each other on the feedback rule. It is important to remember that the way how people behave does not only depend on their social group status. It most importantly is dependent on the type of mind they possess, as well as how they proceed with the learning process and which factors determine their individual neurodevelopmental functions. Human brain is responsible also for some disturbances in their behaviour such as: mastering the skills, assimilating facts or knowledge, carrying out defined actions, working systematical and maintaining in accurate speed, accommodation to scope of requirements, conflicts solving, reading of social information and reacting to them. Premises which are mentioned above show the fact that if we want to be an acting manager in modern company we should know the role of eight neurodevelopmental systems and treat them seriously. We are able to define and create optimal conditions for functioning of every mind and following on to form this friendly, effective organisation in which every employee can work at his own pace, using his own unique knowledge, interests and avocations by knowing his and his associates neurodevelopmental functions and having awareness of existing differences in this scope. In conclusion we can state that the XXIc manager’s role reaches far beyond the tasks which are the essence of the profession (management. It concerns such problems as: interaction optimalization between individual human and his work (good individual preferential accommodation to objective environmental requirements, thus creating advantageous organisational climate, reducing psychological costs of work, decreasing tensions, conflicts and also responsibility

  14. Gestational diabetes mellitus: does an effective prevention strategy exist?

    Science.gov (United States)

    Agha-Jaffar, Rochan; Oliver, Nick; Johnston, Desmond; Robinson, Stephen

    2016-09-01

    The overall incidence of gestational diabetes mellitus (GDM) is increasing worldwide. Preventing pathological hyperglycaemia during pregnancy could have several benefits: a reduction in the immediate adverse outcomes during pregnancy, a reduced risk of long-term sequelae and a decrease in the economic burden to healthcare systems. In this Review we examine the evidence supporting lifestyle modification strategies in women with and without risk factors for GDM, and the efficacy of dietary supplementation and pharmacological approaches to prevent this disease. A high degree of heterogeneity exists between trials so a generalised recommendation is problematic. In population studies of dietary or combined lifestyle measures, risk of developing GDM is not improved and those involving a physical activity intervention have yielded conflicting results. In pregnant women with obesity, dietary modification might reduce fetal macrosomia but in these patients, low compliance and no significant reduction in the incidence of GDM has been observed in trials investigating physical activity. Supplementation with probiotics or myoinositol have reduced the incidence of GDM but confirmatory studies are still needed. In randomized controlled trials, metformin does not prevent GDM in certain at-risk groups. Given the considerable potential for reducing disease burden, further research is needed to identify strategies that can be easily and effectively implemented on a population level.

  15. Pre- and postnatal exposures to pesticides and neurodevelopmental effects in children living in agricultural communities from South-Eastern Spain.

    Science.gov (United States)

    González-Alzaga, Beatriz; Hernández, Antonio F; Rodríguez-Barranco, Miguel; Gómez, Inmaculada; Aguilar-Garduño, Clemente; López-Flores, Inmaculada; Parrón, Tesifón; Lacasaña, Marina

    2015-12-01

    Childrens exposure to neurotoxic compounds poses a major problem to public health because oftheir actively developing brain that makes them highly vulnerable. However, limited information is available on neuropsychological effects in children associated with pre- and postnatal exposures to pesticides. To evaluate the association between current and pre- and postnatal exposures to pesticides and their effects on neurodevelopment in children aged 6–11 years living in agricultural communities from South-Eastern Spain. An ambispective study was conducted on 305 children aged 6–11 years randomly selected from public schools of the study area. Current exposure to organophosphate pesticides was assessed measuring children's urinary levels of dialkylphosphates (DAPs). Both prenatal and postnatal residential exposure to pesticides was estimated by developing a geographical information system (GIS) technology-based index that integrated distance-weighted measure of agricultural surface, time-series of crop areas per municipality and year, and land-use maps. Neuropsychological performance was evaluated with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). The association of pre- and postnatal and current pesticide exposure with WISC-IV scale scores was assessed using multivariate linear regression models and generalized estimating equation (GEE) models, respectively. Greater urinary DAP levels were associated with a poorer performance on intelligence quotient and verbal comprehension domain, with effects being more prominent in boys than in girls. The influence of an increase in 10 ha per year in crop surface around the child's residence during the postnatal period was associated with decreased intelligence quotient, processing speed and verbal comprehension scores. As regards prenatal exposure to pesticides, a poor processing speed performance was observed. These effects were also more prominent in boys than in girls. Our results suggest that

  16. Effects of Donor Breastmilk Feeding on Growth and Early Neurodevelopmental Outcomes in Preterm Infants: An Observational Study.

    Science.gov (United States)

    Madore, Laura S; Bora, Samudragupta; Erdei, Carmina; Jumani, Tina; Dengos, Allison R; Sen, Sarbattama

    2017-06-01

    Donor breastmilk (DBM) has gained popularity as an alternative to formula when mother's own milk (MOM) is unavailable. The objective of this study was to evaluate the effects of a predominantly DBM diet on growth and subsequent neurodevelopment in preterm infants at a level 3 neonatal intensive care unit (NICU). This single-center, observational cohort study compared data from preterm infants supplemented with predominantly (>50%) DBM to those from age- and weight-matched infants fed only MOM or supplemented with predominantly (>50%) preterm formula (PF). The primary outcome was in-hospital weight gain, and the secondary outcome was neurodevelopment, as assessed by the Bayley III scale at 1 and 2 years' corrected age. Exclusion criteria were major congenital defects, death prior to discharge from the NICU, or supplementation volumes of <50% over the first month of life. We compared the outcomes among the 3 feeding groups with the χ 2 test, ANOVA, and ANCOVA, with post hoc pairwise comparisons after adjustment for the following confounders: bronchopulmonary dysplasia, multiple births, and social work involvement. In the entire cohort, the mean gestational age was 27.1 weeks and the mean birthweight was 914 g. The DBM (n = 27) and PF (n = 25) groups were similar with regard to socioeconomic characteristics. DBM infants regained birthweight more slowly over the first month of life compared with infants fed MOM (n = 29) or PF (mean [SD], 17.9 [5.7], 22.0 [6.8], and 20.3 [5.7] g/kg/d, respectively; P = 0.05); however, this growth difference was attenuated at later time points. In a fully adjusted model, the DBM group scored significantly lower in cognition at both 1 year (P = 0.005) and 2 years (P = 0.03) of age compared with the infants fed non-DBM diets. The findings from this study suggest that in this NICU, preterm infants supplemented with predominantly DBM had compromised early in-hospital weight gain and, possibly, early cognitive delays compared with infants

  17. Existence and Policy Effectiveness in Feedback Nash LQ-Games

    Directory of Open Access Journals (Sweden)

    Nicola Acocella

    2008-12-01

    Full Text Available This paper illustrates how the classical theory of economic policy can profitably be used to verify some properties of the Linear Nash Feedback Equilibrium in difference LQ-games. In particular, we find that both a necessary condition for the equilibrium existence and a sufficient condition for policy ineffectiveness can be defined in the terms of the simple Tinbergen counting rule.

  18. Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

    Directory of Open Access Journals (Sweden)

    Nguyen Quoc Vuong Tran

    2017-01-01

    Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.

  19. Adaptation of the "ten questions" to screen for autism and other neurodevelopmental disorders in Uganda.

    Science.gov (United States)

    Kakooza-Mwesige, Angelina; Ssebyala, Keron; Karamagi, Charles; Kiguli, Sarah; Smith, Karen; Anderson, Meredith C; Croen, Lisa A; Trevathan, Edwin; Hansen, Robin; Smith, Daniel; Grether, Judith K

    2014-05-01

    Neurodevelopmental disorders are recognized to be relatively common in developing countries but little data exist for planning effective prevention and intervention strategies. In particular, data on autism spectrum disorders are lacking. For application in Uganda, we developed a 23-question screener (23Q) that includes the Ten Questions screener and additional questions on autism spectrum disorder behaviors. We then conducted household screening of 1169 children, 2-9 years of age, followed by clinical assessment of children who screened positive and a sample of those who screened negative to evaluate the validity of the screener. We found that 320 children (27% of the total) screened positive and 68 children received a clinical diagnosis of one or more moderate to severe neurodevelopmental disorders (autism spectrum disorder; cerebral palsy; epilepsy; cognitive, speech and language, hearing, or vision impairment), including 8 children with autism spectrum disorders. Prevalence and validity of the screener were evaluated under different statistical assumptions. Sensitivity of the 23Q ranged from 0.55 to 0.80 and prevalence for ≥1 neurodevelopmental disorders from 7.7/100 children to 12.8/100 children depending on which assumptions were used. The combination of screening positive on both autism spectrum disorders and Ten Questions items was modestly successful in identifying a subgroup of children at especially high risk of autism spectrum disorders. We recommend that autism spectrum disorders and related behavioral disorders be included in studies of neurodevelopmental disorders in low-resource settings to obtain essential data for planning local and global public health responses.

  20. Neurodevelopmental disorders in children with neurofibromatosis type 1.

    Science.gov (United States)

    Vogel, Alecia C; Gutmann, David H; Morris, Stephanie M

    2017-11-01

    Over the past several decades, neurofibromatosis type 1 (NF1) has become increasingly recognized as a neurodevelopmental disorder conferring increased risk for several important neurodevelopmental problems. In this review, we summarize the specific neurodevelopmental problems encountered in the context of NF1. These include impairments in general cognitive function, deficits in specific cognitive domains such as executive function and visuospatial processing and risk for specific learning disorders, impairments in attention and social skills and the overlap with attention-deficit-hyperactivity disorder and autism spectrum disorder, and the risk of developing other psychiatric conditions including anxiety and depression. Early recognition of these developmental impairments is important for the effective treatment of children with NF1, and further characterization is essential to improve our understanding of how mutations in the NF1 gene create the diversity of clinical neuropsychiatric symptomatology observed in this at-risk population. © 2017 Mac Keith Press.

  1. "Too Withdrawn" or "Too Friendly": Considering Social Vulnerability in Two Neuro-Developmental Disorders

    Science.gov (United States)

    Jawaid, A.; Riby, D. M.; Owens, J.; White, S. W.; Tarar, T.; Schulz, P. E.

    2012-01-01

    In some neuro-developmental disorders, the combined effect of intellectual disability and atypicalities of social cognition may put individuals at increased vulnerability in their social environment. The neuro-developmental disorders Williams syndrome, characterised by "hypersociability", and autism spectrum disorders, characterised by "social…

  2. Neurodevelopmental model of schizophrenia: update 2012

    National Research Council Canada - National Science Library

    Rapoport, J L; Giedd, J N; Gogtay, N

    2012-01-01

    ... greatest potential to modify or extend, the neurodevelopmental model of schizophrenia. Longitudinal whole-population studies support a dimensional, rather than categorical, concept of psychosis...

  3. Testing the effectiveness of existing psycho-educational material ...

    African Journals Online (AJOL)

    Fifteen Setswana speaking participants, with a diagnosis of schizophrenia were exposed to the programme. Semi-structured and screening ... films over formal lectures. Conclusion: Psycho-education material given to people suffering from schizophrenia and their caregivers has to be adapted to their context to be effective.

  4. A compensatory role for declarative memory in neurodevelopmental disorders.

    Science.gov (United States)

    Ullman, Michael T; Pullman, Mariel Y

    2015-04-01

    Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional in these disorders, and because it can learn and retain numerous types of information, functions, and tasks, this system should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Participation in Physical Activity for Children with Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Rubab G. Arim

    2012-01-01

    Full Text Available The purpose of this study was to compare rates of participation for children (4–9 years of age with neurodevelopmental disorders (NDDs with and without externalizing behavior problems (EBPs with children without disability and to examine mediators of the relation between disability and physical activity participation. Data for this study were drawn from Cycle 7 (2006-07 of the Canadian National Longitudinal Survey of Children and Youth (NLSCY. The frequency of children’s participation in organized sports or physical activities varied depending on the child’s health condition with children with NDDs and both NDDs and EBPs participating least in organized sports or physical activities followed by children with EBPs only. In contrast, there were no statistically significant differences by health group for children’s participation in unorganized sports or physical activities. These differences remained even after controlling for the effects of other child and family sociodemographic characteristics, except for children with EBPs only. These findings highlight the importance of considering children’s primary and other existing health conditions as well as family sociodemographic characteristics in order to better understand the factors that influence participation in organized physical activities for children with disabilities.

  6. Sleep in Neurodevelopmental and Neurodegenerative Disorders.

    Science.gov (United States)

    Kotagal, Suresh

    2015-06-01

    There is a close relationship between sleep and childhood neurodevelopmental/neurodegenerative disorders. Understanding the sleep issues may provide greater insight into pathophysiology and treatment of these disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Delayed visual maturation: ophthalmic and neurodevelopmental aspects.

    Science.gov (United States)

    Tresidder, J; Fielder, A R; Nicholson, J

    1990-10-01

    Delayed visual maturation (DVM) can present as an isolated anomaly (type 1A), but can be compounded by perinatal problems (type 1B), severe neurodevelopmental delay (type 2), or ocular anomalies/nystagmus (type 3), in which group the common feature appears to be nystagmus. The neurodevelopmental and ophthalmic aspects of 26 infants with DVM were studied. Onset of visual improvement, rate of acquisition of normal vision and eventual outcome were studied quantitatively, using an adaptation of the acuity card procedure. Neurodevelopmental assessment was performed after visual improvement. The results support the long-held clinical impression that if blindness is the presenting feature, neurodevelopmental outlook is excellent. DVM could represent a defect in the extrageniculostriate visual system, and the onset of vision in all types--and the development of nystagmus in type 3--could herald the emergence of geniculostriate function.

  8. Assisted reproduction and child neurodevelopmental outcomes: a systematic review.

    Science.gov (United States)

    Bay, Bjørn; Mortensen, Erik Lykke; Kesmodel, Ulrik Schiøler

    2013-09-01

    To systematically review the existing literature on neurodevelopmental outcomes in children born after medically assisted reproduction compared with those of children born after spontaneous conception. Systematic review. Not applicable. Children born after medically assisted reproduction vs. reference groups of spontaneously conceived children. Data were reviewed from worldwide published articles, without restrictions as to publication year or language. A total of 80 studies included between 31 and 2,446,044 children. Child neurodevelopmental outcomes categorized as cognitive, behavioral, emotional or psychomotor development, or diagnoses of mental disorders. For infants, studies on psychomotor development showed no deficits, but few investigated cognitive or behavioral development. Studies on toddlers generally reported normal cognitive, behavioral, socio-emotional, and psychomotor development. For children in middle childhood, development seems comparable in children born after assisted reproduction and controls, although fewer studies have been conducted with follow-up to this age. Very few studies have assessed neurodevelopmental outcomes among teens, and the results are inconclusive. Studies investigating the risk of diagnoses of mental disorders are generally large, with long follow-up, but the results are inconsistent. It may tentatively be concluded that the neurodevelopment of children born after fertility treatment is overall comparable to that in children born after spontaneous conception. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. The neurodevelopmental basis of math anxiety.

    Science.gov (United States)

    Young, Christina B; Wu, Sarah S; Menon, Vinod

    2012-05-01

    Math anxiety is a negative emotional reaction to situations involving mathematical problem solving. Math anxiety has a detrimental impact on an individual's long-term professional success, but its neurodevelopmental origins are unknown. In a functional MRI study on 7- to 9-year-old children, we showed that math anxiety was associated with hyperactivity in right amygdala regions that are important for processing negative emotions. In addition, we found that math anxiety was associated with reduced activity in posterior parietal and dorsolateral prefrontal cortex regions involved in mathematical reasoning. Multivariate classification analysis revealed distinct multivoxel activity patterns, which were independent of overall activation levels in the right amygdala. Furthermore, effective connectivity between the amygdala and ventromedial prefrontal cortex regions that regulate negative emotions was elevated in children with math anxiety. These effects were specific to math anxiety and unrelated to general anxiety, intelligence, working memory, or reading ability. Our study identified the neural correlates of math anxiety for the first time, and our findings have significant implications for its early identification and treatment.

  10. Antisocial Personality as a Neurodevelopmental Disorder.

    Science.gov (United States)

    Raine, Adrian

    2018-01-25

    Although antisocial personality disorder (APD) is one of the most researched personality disorders, it is still surprisingly resistant to treatment. This lack of clinical progress may be partly due to the failure to view APD as a neurodevelopmental disorder and to consider early interventions. After first defining what constitutes a neurodevelopmental disorder, this review evaluates the extent to which APD meets neurodevelopmental criteria, covering structural and functional brain imaging, neurocognition, genetics and epigenetics, neurochemistry, and early health risk factors. Prevention and intervention strategies for APD are then outlined, focusing on addressing early biological and health systems, followed by forensic and clinical implications. It is argued both that APD meets criteria for consideration as a neurodevelopmental disorder and that consideration should be given both to the possibility that early onset conduct disorder is neurodevelopmental in nature, and also to the inclusion of psychopathy as a specifier in future Diagnostic and Statistical Manual revisions of APD. Expected final online publication date for the Annual Review of Clinical Psychology Volume 14 is May 7, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  11. GABAergic circuit dysfunctions in neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Bidisha eChattopadhyaya

    2012-05-01

    Full Text Available GABAergic interneurons control neuronal excitability, integration, and plasticity. Further, they regulate the generation of temporal synchrony and oscillatory behavior among networks of pyramidal neurons. Such oscillations within and across neural systems are believed to serve various complex functions, such as perception, movement initiation, and memory. Alterations in the development of GABAergic circuits have been implicated in various brain diseases with neurodevelopmental origin. Here, we highlight recent studies suggesting a role for alterations of GABA transmission in the pathophysiology of two neurodevelopmental diseases, schizophrenia and autism. We further discuss how manipulations of GABA signaling may be used for novel therapeutic interventions.

  12. Neurodevelopmental consequences of being born SGA

    NARCIS (Netherlands)

    van Wassenaer, Aleid

    2005-01-01

    Fetal growth retardation is associated with postnatal growth retardation and cardio-vascular and metabolic problems later on in life. Less well described are the consequences of neurodevelopmental outcome. The term SGA is associated with mild to moderate school problems, still present in late

  13. Neurodevelopmental Outcomes of Children with Periventricular Leukomalacia

    Directory of Open Access Journals (Sweden)

    Takashi Imamura

    2013-12-01

    Conclusion: Most children with grade 2 or 3 PVL had severe neurodevelopmental delays, but attention should also be paid to the 56% of children with grade 1 PVL who presented with normal psychomotor development. Further studies of larger populations, including long-term follow-up, are necessary to evaluate the outcomes of children with PVL.

  14. School Neuropsychology Consultation in Neurodevelopmental Disorders

    Science.gov (United States)

    Decker, Scott L.

    2008-01-01

    The role of school psychologists with training in neuropsychology is examined within the context of multitiered models of service delivery and educational reform policies. An expanded role is suggested that builds on expertise in the assessment of neurodevelopmental disorders and extends to broader tiers through consultation practice. Changes in…

  15. Drosophila Modeling of Heritable Neurodevelopmental Disorders

    OpenAIRE

    Gatto, Cheryl L.; Broadie, Kendal

    2011-01-01

    Heritable neurodevelopmental disorders are multifaceted disease conditions encompassing a wide range of symptoms including intellectual disability, cognitive dysfunction, autism and myriad other behavioral impairments. In cases where single, causative genetic defects have been identified, such as Angelman syndrome, Rett syndrome, Neurofibromatosis Type 1 and Fragile X syndrome, the classical Drosophila genetic system has provided fruitful disease models. Recent Drosophila studies have advance...

  16. Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome.

    Science.gov (United States)

    Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L

    2012-04-01

    The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.

  17. The Response of Old Technology Incumbents to Technological Competition - Does the Sailing Ship Effect Exist?

    DEFF Research Database (Denmark)

    Howells, John

    This article investigates whether firms react to a radical technological substitution threat by a deliberate acceleration of innovation in their existing technology - the 'sailing ship effect'. It has been argued that the effect is both significant and widespread and warrants a reexamination of our...

  18. The Functional Evaluation of Eating Difficulties Scale: Study Protocol and Validation in Infants with Neurodevelopmental Impairments and Disabilities

    Directory of Open Access Journals (Sweden)

    Anna Cavallini

    2017-12-01

    Full Text Available IntroductionA reliable and accurate evaluation of oral-motor skills in newborns at risk for swallowing and feeding disorders is key to set the goals of effective early interventions. Although many tools are available to assess oral-motor skills in newborns, limited evidence exists for what pertains their reliability and their effectivity in predicting short- and long-term developmental outcomes in at-risk infants. The aim of the present study is to develop and provide a preliminary validation of a new clinically grounded tool [i.e., the Functional Evaluation of Eating Difficulties Scale (FEEDS] specifically designed to be used with at-risk newborns and infants. The paper describes the steps of tool development and information on the reliability of the tool are provided.Methods/analysisThe FEEDS has been developed according to clinical evidence and expertise by a multidisciplinary team of professionals dealing with feeding problems in at-risk infants diagnosed with neurodevelopmental impairments and disabilities. The steps of FEEDS development are reported, together with a detailed description of items, scoring procedure, and clinical cutoff. The FEEDS has been applied to a relatively large sample of 0- to 12-month-old infants (N = 136 with neurodevelopmental disability, enrolled consecutively between 2004 and 2016 at the Scientific Institute IRCCS Eugenio Medea (Bosisio Parini, Italy, which is the main rehabilitation hospital for children with neurodevelopmental disabilities in Italy. Internal consistency (Cronbach’s alpha and reliability (inter-rater agreement have been assessed.Ethics and disseminationAll the procedures are consistent with the World Medical Association Declaration of Helsinki (2013 and the FEEDS has been approved by the clinical committee of the Scientific Institute IRCCS Eugenio Medea. Further psychometric characteristics and evidence of the predictive validity of the FEEDS will be obtained on a larger sample and they

  19. The Functional Evaluation of Eating Difficulties Scale: Study Protocol and Validation in Infants with Neurodevelopmental Impairments and Disabilities.

    Science.gov (United States)

    Cavallini, Anna; Provenzi, Livio; Sacchi, Daniela; Longoni, Laura; Borgatti, Renato

    2017-01-01

    A reliable and accurate evaluation of oral-motor skills in newborns at risk for swallowing and feeding disorders is key to set the goals of effective early interventions. Although many tools are available to assess oral-motor skills in newborns, limited evidence exists for what pertains their reliability and their effectivity in predicting short- and long-term developmental outcomes in at-risk infants. The aim of the present study is to develop and provide a preliminary validation of a new clinically grounded tool [i.e., the Functional Evaluation of Eating Difficulties Scale (FEEDS)] specifically designed to be used with at-risk newborns and infants. The paper describes the steps of tool development and information on the reliability of the tool are provided. The FEEDS has been developed according to clinical evidence and expertise by a multidisciplinary team of professionals dealing with feeding problems in at-risk infants diagnosed with neurodevelopmental impairments and disabilities. The steps of FEEDS development are reported, together with a detailed description of items, scoring procedure, and clinical cutoff. The FEEDS has been applied to a relatively large sample of 0- to 12-month-old infants ( N  = 136) with neurodevelopmental disability, enrolled consecutively between 2004 and 2016 at the Scientific Institute IRCCS Eugenio Medea (Bosisio Parini, Italy), which is the main rehabilitation hospital for children with neurodevelopmental disabilities in Italy. Internal consistency (Cronbach's alpha) and reliability (inter-rater agreement) have been assessed. All the procedures are consistent with the World Medical Association Declaration of Helsinki (2013) and the FEEDS has been approved by the clinical committee of the Scientific Institute IRCCS Eugenio Medea. Further psychometric characteristics and evidence of the predictive validity of the FEEDS will be obtained on a larger sample and they will be reported in future publications from this group.

  20. Histone Lysine Methylation and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Jeong-Hoon Kim

    2017-06-01

    Full Text Available Methylation of several lysine residues of histones is a crucial mechanism for relatively long-term regulation of genomic activity. Recent molecular biological studies have demonstrated that the function of histone methylation is more diverse and complex than previously thought. Moreover, studies using newly available genomics techniques, such as exome sequencing, have identified an increasing number of histone lysine methylation-related genes as intellectual disability-associated genes, which highlights the importance of accurate control of histone methylation during neurogenesis. However, given the functional diversity and complexity of histone methylation within the cell, the study of the molecular basis of histone methylation-related neurodevelopmental disorders is currently still in its infancy. Here, we review the latest studies that revealed the pathological implications of alterations in histone methylation status in the context of various neurodevelopmental disorders and propose possible therapeutic application of epigenetic compounds regulating histone methylation status for the treatment of these diseases.

  1. Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm.

    Science.gov (United States)

    Qin, Gordon; Lo, Jessica W; Marlow, Neil; Calvert, Sandy A; Greenough, Anne; Peacock, Janet L

    2017-01-01

    Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities.

  2. Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting.

    Science.gov (United States)

    Velazquez, Victoria M; Meadows, Aaron S; Pineda, Ricardo J; Camboni, Marybeth; McCarty, Douglas M; Fu, Haiyan

    2017-03-17

    Pre-existing antibodies (Abs) to AAV pose a critical challenge for the translation of gene therapies. No effective approach is available to overcome pre-existing Abs. Given the complexity of Ab production, overcoming pre-existing Abs will require broad immune targeting. We generated a mouse model of pre-existing AAV9 Abs to test multiple immunosuppressants, including bortezomib, rapamycin, and prednisolone, individually or in combination. We identified an effective approach combining rapamycin and prednisolone, reducing serum AAV9 Abs by 70%-80% at 4 weeks and 85%-93% at 8 weeks of treatment. The rapamycin plus prednisolone treatment resulted in significant decreases in the frequency of B cells, plasma cells, and IgG-secreting and AAV9-specific Ab-producing plasma cells in bone marrow. The rapamycin plus prednisolone treatment also significantly reduced frequencies of IgD-IgG+ class-switched/FAS+CL7+ germinal center B cells, and of activated CD4+ T cells expressing PD1 and GL7, in spleen. These data suggest that rapamycin plus prednisolone has selective inhibitory effects on both T helper type 2 support of B cell activation in spleen and on bone marrow plasma cell survival, leading to effective AAV9 Abs depletion. This promising immunomodulation approach is highly translatable, and it poses minimal risk in the context of therapeutic benefits promised by gene therapy for severe monogenetic diseases, with a single or possibly a few treatments over a lifetime.

  3. Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting

    Directory of Open Access Journals (Sweden)

    Victoria M. Velazquez

    2017-03-01

    Full Text Available Pre-existing antibodies (Abs to AAV pose a critical challenge for the translation of gene therapies. No effective approach is available to overcome pre-existing Abs. Given the complexity of Ab production, overcoming pre-existing Abs will require broad immune targeting. We generated a mouse model of pre-existing AAV9 Abs to test multiple immunosuppressants, including bortezomib, rapamycin, and prednisolone, individually or in combination. We identified an effective approach combining rapamycin and prednisolone, reducing serum AAV9 Abs by 70%–80% at 4 weeks and 85%–93% at 8 weeks of treatment. The rapamycin plus prednisolone treatment resulted in significant decreases in the frequency of B cells, plasma cells, and IgG-secreting and AAV9-specific Ab-producing plasma cells in bone marrow. The rapamycin plus prednisolone treatment also significantly reduced frequencies of IgD−IgG+ class-switched/FAS+CL7+ germinal center B cells, and of activated CD4+ T cells expressing PD1 and GL7, in spleen. These data suggest that rapamycin plus prednisolone has selective inhibitory effects on both T helper type 2 support of B cell activation in spleen and on bone marrow plasma cell survival, leading to effective AAV9 Abs depletion. This promising immunomodulation approach is highly translatable, and it poses minimal risk in the context of therapeutic benefits promised by gene therapy for severe monogenetic diseases, with a single or possibly a few treatments over a lifetime.

  4. Using an Electronic Highlighter to Eliminate the Negative Effects of Pre-Existing, Inappropriate Highlighting

    Science.gov (United States)

    Gier, Vicki; Kreiner, David; Hudnell, Jason; Montoya, Jodi; Herring, Daniel

    2011-01-01

    The purpose of the present experiment was to determine whether using an active learning technique, electronic highlighting, can eliminate the negative effects of pre-existing, poor highlighting on reading comprehension. Participants read passages containing no highlighting, appropriate highlighting, or inappropriate highlighting. We hypothesized…

  5. Existence Results for a Coupled System of Nonlinear Singular Fractional Differential Equations with Impulse Effects

    Directory of Open Access Journals (Sweden)

    Yuji Liu

    2013-01-01

    Full Text Available A boundary value problem for the singular fractional differential system with impulse effects is presented. By applying Schauder's fixed point theorem in a suitably Banach space, we obtain the existence of at least one solution for this problem. Two examples are presented to illustrate the main theorem.

  6. The cerebellum and neurodevelopmental disorders

    Science.gov (United States)

    Stoodley, Catherine J.

    2015-01-01

    Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior. PMID:26298473

  7. The Cerebellum and Neurodevelopmental Disorders.

    Science.gov (United States)

    Stoodley, Catherine J

    2016-02-01

    Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior.

  8. Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Kunio Miyake

    2012-04-01

    Full Text Available The number of children with mild neurodevelopmental disorders, such as autism, has been recently increasing in advanced countries. This increase is probably caused by environmental factors rather than genetic factors, because it is unlikely that genetic mutation rates suddenly increased within a short period. Epigenetics is a mechanism that regulates gene expression, depending not on the underlying DNA sequence but on the chemical modifications of DNA and histone proteins. Because mental stress can alter the epigenetic status in neuronal cells, environmental factors may alter brain function through epigenetic changes. However, one advantage of epigenetic changes is their reversibility. Therefore, diseases due to abnormal epigenetic regulation are theoretically treatable. In fact, several drugs for treating mental diseases are known to have restoring effects on aberrant epigenetic statuses, and a novel therapeutic strategy targeting gene has been developed. In this review, we discuss epigenetic mechanisms of congenital and acquired neurodevelopmental disorders, drugs with epigenetic effects, novel therapeutic strategies for epigenetic diseases, and future perspectives in epigenetic medicine.

  9. The sea urchin, Paracentrotus lividus, embryo as a "bioethical" model for neurodevelopmental toxicity testing: effects of diazinon on the intracellular distribution of OTX2-like proteins.

    Science.gov (United States)

    Aluigi, M G; Angelini, C; Corte, G; Falugi, C

    2008-12-01

    Presently, a large effort is being made worldwide to increase the sustainability of industrial development, while preserving not only the quality of the environment but also that of animal and human life. In this work, sea urchin early developmental stages were used as a model to test the effects of the organophosphate pesticide (diazinon) on the regulation of gene expression by immunohistochemical localization of the human regulatory protein against the human OTX2. Egg exposure to diazinon did not affect fertilization; however, at concentrations 10(-5)-10(-6) M, it did cause developmental anomalies, among which was the dose-dependent alteration of the intracellular distribution of a regulatory protein that is immunologically related to the human OTX2. The severe anomalies and developmental delay observed after treatment at 10(-5) M concentration are indicators of systemic toxicity, while the results after treatment at 10(-6) M suggest a specific action of the neurotoxic compound. In this second case, exposure to diazinon caused partial delivery of the protein into the nuclei, a defective translocation that particularly affected the blastula and gastrula stages. Therefore, the possibility that neurotoxic agents such as organophosphates may damage embryonic development is taken into account. Specifically, the compounds are known to alter cytoplasmic dynamics, which play a crucial role in regulating the distribution of intracellular structures and molecules, as well as transcription factors. Speculatively, basing our assumptions on Fura2 experiments, we submit the hypothesis that this effect may be due to altered calcium dynamics, which in turn alter cytoskeleton dynamics: the asters, in fact, appear strongly positive to the OTX2 immunoreaction, in both control and exposed samples. Coimmunoprecipitation experiments seem to supply evidence to the hypothesis.

  10. Assessing quality of nursing care as a confounding variable in an outcome study on Neurodevelopmental treatment

    NARCIS (Netherlands)

    L. van der Weide; M.H.F. Grypdonck; Dr. T.B. Hafsteinsdóttir; K. Strijker; C. Kruitwagen

    2007-01-01

    When planning a study measuring the effects of a neurodevelopmental treatment (NDT), we were confronted with the methodological problem that while measuring the effects of NDT, a rival hypothesis is that the decision to implement the NDT might be related to the quality of nursing care. Therefore, we

  11. Practitioner Review: Multilingualism and neurodevelopmental disorders - an overview of recent research and discussion of clinical implications.

    Science.gov (United States)

    Uljarević, Mirko; Katsos, Napoleon; Hudry, Kristelle; Gibson, Jenny L

    2016-11-01

    Language and communication skills are essential aspects of child development, which are often disrupted in children with neurodevelopmental disorders. Cutting edge research in psycholinguistics suggests that multilingualism has potential to influence social, linguistic and cognitive development. Thus, multilingualism has implications for clinical assessment, diagnostic formulation, intervention and support offered to families. We present a systematic review and synthesis of the effects of multilingualism for children with neurodevelopmental disorders and discuss clinical implications. We conducted systematic searches for studies on multilingualism in neurodevelopmental disorders. Keywords for neurodevelopmental disorders were based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition categories as follows; Intellectual Disabilities, Communication Disorders, Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder, Specific Learning Disorder, Motor Disorders, Other Neurodevelopmental Disorders. We included only studies based on empirical research and published in peer-reviewed journals. Fifty studies met inclusion criteria. Thirty-eight studies explored multilingualism in Communication Disorders, 10 in ASD and two in Intellectual Disability. No studies on multilingualism in Specific Learning Disorder or Motor Disorders were identified. Studies which found a disadvantage for multilingual children with neurodevelopmental disorders were rare, and there appears little reason to assume that multilingualism has negative effects on various aspects of functioning across a range of conditions. In fact, when considering only those studies which have compared a multilingual group with developmental disorders to a monolingual group with similar disorders, the findings consistently show no adverse effects on language development or other aspects of functioning. In the case of ASD, a positive effect on communication and social functioning has

  12. Two-year neurodevelopmental outcomes of ventilated preterm infants treated with inhaled nitric oxide.

    Science.gov (United States)

    Walsh, Michele C; Hibbs, Anna Maria; Martin, Camilia R; Cnaan, Avital; Keller, Roberta L; Vittinghoff, Eric; Martin, Richard J; Truog, William E; Ballard, Philip L; Zadell, Arlene; Wadlinger, Sandra R; Coburn, Christine E; Ballard, Roberta A

    2010-04-01

    In a randomized multi-center trial, we demonstrated that inhaled nitric oxide begun between 7 and 21 days and given for 24 days significantly increased survival without bronchopulmonary dysplasia (BPD) in ventilated premature infants weighing score <70 on the Bayley Scales II), compared with 114 of 234 (49%) in the placebo group (relative risk, 0.92; 95% CI, 0.75-1.12; P = .39). No differences on any subcomponent of neurodevelopmental impairment or growth variables were found between inhaled nitric oxide or placebo. Inhaled nitric oxide improved survival free of BPD, with no adverse neurodevelopmental effects at 2 years of age. Copyright 2010 Mosby, Inc. All rights reserved.

  13. Neurodevelopmental pathways to preterm children's specific and general mathematic abilities.

    Science.gov (United States)

    Jaekel, Julia; Bartmann, Peter; Schneider, Wolfgang; Wolke, Dieter

    2014-10-01

    Preterm children have problems with mathematics but knowledge about the predictors of specific mathematic abilities in preterm populations is scarce. This study investigated neurodevelopmental pathways to children's general and specific mathematic abilities across the full gestational age range. Prospective geographically defined longitudinal investigation in Germany. 947 children across the full gestational age range (23-41 weeks). Outcome measures. At 8 years, children's cognitive and mathematic abilities were measured and residuals of a regression predicting mathematic scores by IQ were used to identify specific mathematic abilities. Neurodevelopmental cascade models revealed that adverse effects of preterm birth on mathematic abilities were mediated by neonatal risk. Specific mathematic abilities were uniquely predicted by the duration of hospitalization and ventilation. Prolonged neonatal medical treatment and, in particular, mechanical ventilation may lead to specific impairments in mathematic tasks. These findings have implications for the mode of respiratory support in neonates, routine follow-up and intervention planning as well as research about brain reorganization after preterm birth. Copyright © 2014. Published by Elsevier Ireland Ltd.

  14. Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

    Directory of Open Access Journals (Sweden)

    Muneko Nishijo

    Full Text Available In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1 a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2 a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3 a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4 a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits

  15. Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

    Science.gov (United States)

    Nishijo, Muneko; Tai, Pham The; Anh, Nguyen Thi Nguyet; Nghi, Tran Ngoc; Nakagawa, Hideaki; Van Luong, Hoang; Anh, Tran Hai; Morikawa, Yuko; Waseda, Tomoo; Kido, Teruhiko; Nishijo, Hisao

    2015-01-01

    In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that

  16. Gender specific differences in neurodevelopmental effects of prenatal exposure to very low-lead levels: the prospective cohort study in three-year olds.

    Science.gov (United States)

    Jedrychowski, Wieslaw; Perera, Frederica; Jankowski, Jeffery; Mrozek-Budzyn, Dorota; Mroz, Elzbieta; Flak, Elzbieta; Edwards, Susan; Skarupa, Anita; Lisowska-Miszczyk, Ilona

    2009-08-01

    The primary purpose of this study was to assess the relationship between very low-level of prenatal lead exposure measured in the cord blood (Development Index (MDI). The study sample consisted of 457 children born to non-smoking women living in the inner city and the outlying residential areas of Krakow. The relationship between prenatal lead exposure and MDI scores measured at 12, 24 and 36 months of age and adjusted to a set of important covariates (gender of child, maternal education, parity, breastfeeding, prenatal and postnatal environmental tobacco smoke) was evaluated with linear multivariate regression, and the Generalized Estimating Equations (GEE) longitudinal panel model. The median of lead level in cord blood was 1.21 microg/dL with the range of values from 0.44 to 4.60 microg/dL. Neither prenatal BLL (dichotomized by median) nor other covariates affected MDI score at 12 months of age. Subsequent testing of children at 24 months of age showed a borderline significant inverse association of lead exposure and mental function (beta coefficient=-2.42, 95%CI: -4.90 to 0.03), but the interaction term (BLL x male gender) was not significant. At 36 months, prenatal lead exposure was inversely and significantly associated with cognitive function in boys (Spearman correlation coefficient=-0.239, p=0.0007) but not girls (r=-0.058, p=0.432) and the interaction between BLL and male gender was significant (beta coefficient=-4.46; 95%CI: -8.28 to -0.63). Adjusted estimates of MDI deficit in boys at 36 months confirmed very strong negative impact of prenatal lead exposure (BLL>1.67 microg/dL) compared with the lowest quartile of exposure (beta coefficient=-6.2, p=0.002), but the effect in girls was insignificant (beta coefficient=-0.74, p=0.720). The average deficit of cognitive function in the total sample over the first three years of life (GEE model) associated with higher prenatal lead exposure was also significant (beta coefficient=-3.00; 95%CI: -5.22 to -0

  17. Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: How can we delineate causal effects?

    Science.gov (United States)

    Ponsonby, Anne-Louise; Symeonides, Christos; Vuillermin, Peter; Mueller, Jochen; Sly, Peter D; Saffery, Richard

    2016-07-01

    Accumulating evidence, from animal models and human observational studies, implicates the in utero (and early postnatal) environment in the 'programming' of risk for a variety of adverse outcomes and health trajectories. The modern environment is replete with man-made compounds such as plastic product chemicals (PPC), including phenols and phthalates. Evidence from several human cohorts implicates exposure to these chemicals in adverse offspring neurodevelopment, though a direct causal relationship has not been firmly established. In this review we consider a potential causal pathway that encompasses epigenetic human variation, and how we might test this mechanistic hypothesis in human studies. In the first part of this report we outline how PPCs induce epigenetic change, focusing on the brain derived neurotrophic factor (BDNF) gene, a key regulator of neurodevelopment. Further, we discuss the role of the epigenetics of BDNF and other genes in neurodevelopment and the emerging human evidence of an association between phthalate exposure and adverse offspring neurodevelopment. We discuss aspects of epidemiological and molecular study design and analysis that could be employed to strengthen the level of human evidence to infer causality. We undertake this using an exemplar recent research example: maternal prenatal smoking, linked to methylation change at the aryl hydrocarbon receptor repressor (AHRR) gene at birth, now shown to mediate some of the effects of maternal smoking on birth weight. Characterizing the relationship between the modern environment and the human molecular pathways underpinning its impact on early development is paramount to understanding the public health significance of modern day chemical exposures. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. International telemedicine consultations for neurodevelopmental disabilities.

    Science.gov (United States)

    Pearl, Phillip L; Sable, Craig; Evans, Sarah; Knight, Joseph; Cunningham, Parker; Lotrecchiano, Gaetano R; Gropman, Andrea; Stuart, Sheela; Glass, Penny; Conway, Anne; Ramadan, Issam; Paiva, Tania; Batshaw, Mark L; Packer, Roger J

    2014-06-01

    A telemedicine program was developed between the Children's National Medical Center (CNMC) in Washington, DC, and the Sheikh Khalifa Bin Zayed Foundation in the United Arab Emirates (UAE). A needs assessment and a curriculum of on-site training conferences were devised preparatory to an ongoing telemedicine consultation program for children with neurodevelopmental disabilities in the underserved eastern region of the UAE. Weekly telemedicine consultations are provided by a multidisciplinary faculty. Patients are presented in the UAE with their therapists and families. Real-time (video over Internet protocol; average connection, 768 kilobits/s) telemedicine conferences are held weekly following previews of medical records. A full consultation report follows each telemedicine session. Between February 29, 2012 and June 26, 2013, 48 weekly 1-h live interactive telemedicine consultations were conducted on 48 patients (28 males, 20 females; age range, 8 months-22 years; median age, 5.4 years). The primary diagnoses were cerebral palsy, neurogenetic disorders, autism, neuromuscular disorders, congenital anomalies, global developmental delay, systemic disease, and epilepsy. Common comorbidities were cognitive impairment, communication disorders, and behavioral disorders. Specific recommendations included imaging and DNA studies, antiseizure management, spasticity management including botulinum toxin protocols, and specific therapy modalities including taping techniques, customized body vests, and speech/language and behavioral therapy. Improved outcomes reported were in clinician satisfaction, achievement of therapy goals for patients, and requests for ongoing sessions. Weekly telemedicine sessions coupled with triannual training conferences were successfully implemented in a clinical program dedicated to patients with neurodevelopmental disabilities by the Center for Neuroscience at CNMC and the UAE government. International consultations in neurodevelopmental

  19. The “healthy immigrant” effect: does it exist in Europe today?

    Directory of Open Access Journals (Sweden)

    Alexander Domnich

    2012-09-01

    Full Text Available Several studies, carried out mainly in the United States and Canada, have suggested that recent immigrants are generally healthier than native-born populations in spite of the fact that they frequently have a lower socioeconomic status and less access to healthcare services. This “epidemiological paradox” has been called the “healthy immigrant” effect and is usually attributed to a self-selection process prior to migration, “cultural buffering” and official health screening and employability in receiving countries. In this paper, we have evaluated the European scientific research into the existence of the “healthy immigrant” effect.

  20. Neurodevelopmental outcomes in children with congenital hypothyroidism

    OpenAIRE

    Almeida, Carolina Lopes de

    2016-01-01

    Trabalho de revisão do 6º ano médico com vista à atribuição do grau de mestre (área científica de pediatria) no âmbito do ciclo de estudos de Mestrado Integrado em Medicina. Although prognosis of Congenital Hypothyroidism (CH) has been greatly modified since the introduction of newborn screening programs, persistent cognitive deficits are still reported. The aim of this study was to evaluate neurodevelopmental outcomes of children with CH and to determine whether severity of CH, age of...

  1. Drosophila modeling of heritable neurodevelopmental disorders.

    Science.gov (United States)

    Gatto, Cheryl L; Broadie, Kendal

    2011-12-01

    Heritable neurodevelopmental disorders are multifaceted disease conditions encompassing a wide range of symptoms including intellectual disability, cognitive dysfunction, autism and myriad other behavioral impairments. In cases where single, causative genetic defects have been identified, such as Angelman syndrome, Rett syndrome, Neurofibromatosis Type 1 and Fragile X syndrome, the classical Drosophila genetic system has provided fruitful disease models. Recent Drosophila studies have advanced our understanding of UBE3A, MECP2, NF1 and FMR1 function, respectively, in genetic, biochemical, anatomical, physiological and behavioral contexts. Investigations in Drosophila continue to provide the essential mechanistic understanding required to facilitate the conception of rational therapeutic treatments. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Effects of Active Subsidence Vs. Existing Basin Geometry on Fluviodeltaic Channels and Stratal Architecture

    Science.gov (United States)

    Liang, M.; Kim, W.; Passalacqua, P.

    2015-12-01

    Tectonic subsidence and basin topography, both determining the accommodation, are fundamental controls on the basin filling processes. Their effects on the fluvial organization and the resultant subsurface patterns remain difficult to predict due to the lack of understanding about interaction between internal dynamics and external controls. Despite the intensive studies on tectonic steering effects on alluvial architecture, how the self-organization of deltaic channels, especially the distributary channel network, respond to tectonics and basin geometry is mostly unknown. Recently physical experiments and field studies have hinted dramatic differences in fluviodeltaic evolution between ones associated with active differential subsidence and existing basin depth. In this work we designed a series of numerical experiments using a reduced-complexity channel-resolving model for delta formation, and tested over a range of localized subsidence rates and topographic depression in basin geometry. We also used a set of robust delta metrics to analyze: i) shoreline planform asymmetry, ii) channel and lobe geometry, iii) channel network pattern, iv) autogenic timescales, and v) subsurface structure. The modeling results show that given a similar final thickness, active subsidence enhances channel branching with smaller channel sand bodies that are both laterally and vertically connected, whereas existing topographic depression causes more large-scale channel avulsions with larger channel sand bodies. In general, both subsidence and existing basin geometry could steer channels and/or lock channels in place but develop distinct channel patterns and thus stratal architecture.

  3. Improvement of effectiveness of existing Casuarina equisetifolia forests in mitigating tsunami damage.

    Science.gov (United States)

    Samarakoon, M B; Tanaka, Norio; Iimura, Kosuke

    2013-01-15

    Coastal vegetation can play a significant role in reducing the severity of a tsunami because the energy associated with the tsunami is dissipated when it passes through coastal vegetation. Field surveys were conducted on the eastern coastline of Sri Lanka to investigate which vegetation species are effective against a tsunami and to evaluate the effectiveness of existing Casuarina equisetifolia forests in tsunami mitigation. Open gaps in C. equisetifolia forests were identified as a disadvantage, and introduction of a new vegetation belt in front or back of the existing C. equisetifolia forest is proposed to reduce the disadvantages of the open gap. Among the many plant species encountered during the field survey, ten species were selected as effective for tsunami disaster mitigation. The selection of appropriate vegetation for the front or back vegetation layer was based on the vegetation thickness per unit area (dN(u)) and breaking moment of each species. A numerical model based on two-dimensional nonlinear long-wave equations was applied to explain the present situation of open gaps in C. equisetifolia forests, and to evaluate the effectiveness of combined vegetation systems. The results of the numerical simulation for existing conditions of C. equisetifolia forests revealed that the tsunami force ratio (R = tsunami force with vegetation/tsunami force without vegetation) was 1.4 at the gap exit. The species selected for the front and back vegetation layers were Pandanus odoratissimus and Manilkara hexandra, respectively. A numerical simulation of the modified system revealed that R was reduced to 0.7 in the combined P. odoratissimus and C. equisetifolia system. However, the combination of C. equisetifolia and M. hexandra did not effectively reduce R at the gap exit. Therefore, P. odoratissimus as the front vegetation layer is proposed to reduce the disadvantages of the open gaps in existing C. equisetifolia forests. The optimal width of P. odoratissimus (W(1

  4. No association between transient hypothyroxinaemia of prematurity and neurodevelopmental outcome in young adulthood

    NARCIS (Netherlands)

    Hollanders, J.J.; Israëls, J.; Pal, S.M. van der; Verkerk, P.H.; Rotteveel, J.; Finken, M.J.J.; Hille, E.T.M.; Groot, C.H. de; Kloosterboer-Boerrigter, H.; Ouden, A.L. den; Rijpstra, A.; Verloove-Vanhorick, S.P.; Vogelaar, J.A.; Kok, J.H.; Ilsen, A.; Lans, M. van der; Boelen-Van Der Loo, W.J.C.; Lundqvist, T.; Heymans, H.S.A.; Duiverman, E.J.; Geven, W.B.; Duiverman, M.L.; Geven, L.I.; Vrijlandt, E.J.L.E.; Mulder, A.L.M.; Gerver, A.; Kollée, L.A.A.; Reijmers, L.; Sonnemans, R.; Wit, J.M.; Dekker, F.W.; Weisglas-Kuperus, N.; Heijden, A.J. van der; Goudoever, J.B. van; Weissenbruch, M.M. van; Cranendonk, A.; Delemarre-Van De Waal, H.A.; Groot, L. de; Samsom, J.F.; Vries, L.S. de; Rademaker, K.J.; Moerman, E.; Voogsgeerd, M.; Kleine, M.J.K. de; Andriessen, P.; Dielissen-Van Helvoirt, C.C.M.; Mohamed, I.; Straaten, H.L.M. van; Baerts, W.; Veneklaas Slots-Kloosterboer, G.W.; Tuller-Pikkemaat, E.M.J.; Ens-Dokkum, M.H.; Steenbrugge, G.J. van

    2015-01-01

    Context: Transient hypothyroxinaemia of prematurity (THoP) has been associated with neurodevelopmental impairment in infancy and childhood. It is not known whether these relations persist into adulthood. Objective: To examine whether there is an effect of THoP on intelligence quotient (IQ) score and

  5. Neurodevelopmental Disorders in Children with Severe to Profound Sensorineural Hearing Loss: A Clinical Study

    Science.gov (United States)

    Chilosi, Anna M.; Comparini, Alessandro; Scusa, Maria F.; Berrettini, Stefano; Forli, Francesca; Battini, Roberta; Cipriani, Paola; Cioni, Giovanni

    2010-01-01

    Aim: The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation…

  6. Neurodevelopmental Outcomes in Very Low Birth Weight Infants Using Aminophylline for the Treatment of Apnea

    Directory of Open Access Journals (Sweden)

    Shu-Leei Tey

    2016-02-01

    Conclusion: Aminophylline therapy for apnea of prematurity had no apparent and additional risk on the neurodevelopmental outcomes of VLBW infants at a corrected age of 18 months. Further studies with a larger sample size are needed to confirm the adverse neurological effects of aminophylline treatment.

  7. A Note on the Existence of the Posteriors for One-way Random Effect Probit Models.

    Science.gov (United States)

    Lin, Xiaoyan; Sun, Dongchu

    2010-01-01

    The existence of the posterior distribution for one-way random effect probit models has been investigated when the uniform prior is applied to the overall mean and a class of noninformative priors are applied to the variance parameter. The sufficient conditions to ensure the propriety of the posterior are given for the cases with replicates at some factor levels. It is shown that the posterior distribution is never proper if there is only one observation at each factor level. For this case, however, a class of proper priors for the variance parameter can provide the necessary and sufficient conditions for the propriety of the posterior.

  8. A Novel Adaptive Beamformer for MEG Source Reconstruction Effective When Large Background Brain Activities Exist

    Science.gov (United States)

    Sekihara, Kensuke; Hild, Kenneth E.; Nagarajan, Srikantan S.

    2014-01-01

    This paper proposes a novel prewhitening eigenspace beamformer suitable for magnetoencephalogram (MEG) source reconstruction when large background brain activities exist. The prerequisite for the method is that control-state measurements, which contain only the contributions from the background interference, be available, and that the covariance matrix of the background interference can be obtained from such control-state measurements. The proposed method then uses this interference covariance matrix to remove the influence of the interference in the reconstruction obtained from the target measurements. A numerical example, as well as applications to two types of MEG data, demonstrates the effectiveness of the proposed method. PMID:16941831

  9. Yield of additional metabolic studies in neurodevelopmental disorders

    NARCIS (Netherlands)

    Engbers, Hannelie M; Berger, Ruud; van Hasselt, Peter; de Koning, Tom; de Sain-van der Velden, Monique G M; Kroes, Hester Y; Visser, Gepke

    The timing and yield of metabolic studies for patients with neurodevelopmental disorders is a matter of continuing debate. We determined the yield of additional or repeated metabolic studies in patients with neurodevelopmental disorders. Patients referred to a tertiary diagnostic center for patients

  10. Preoperative electrocardiography: its cost-effectiveness in detecting abnormalities when a previous tracing exists.

    Science.gov (United States)

    Rabkin, S W; Horne, J M

    1979-01-01

    In 812 patients who underwent routine preoperative electrocardiography a mean of 24.6 months after undergoing electrocardiography at the same institution, the frequency of new abnormalities was estimated to evaluate the cost-effectiveness of this procedure prior to an operation. New abnormalities were judged to be either relevant or irrelevant to the assessment of operative risk, depending upon their previously demonstrated correlation with operative and postoperative morbidity and mortality. Since new abnormalities, especially new relevant abnormalities, were found to be relatively infrequent, the cost-effectiveness of routine preoperative electrocardiography was considered to be low. The evidence suggested that when a previous tracing exists preoperative electrocardiography is most clearly indicated for patients who are 60 years of age or older or whose previous tracing exhibited abnormalities. However, further research is required to develop more sensitive and specific protocols, and to evaluate the role of repeat electrocardiography in clinical decision-making. PMID:111793

  11. PRIVATE LAW EFFECTS OF THE NON-RECOGNITION OF STATES' EXISTENCE AND TERRITORIAL CHANGES

    Directory of Open Access Journals (Sweden)

    Ioan-Luca VLAD

    2015-07-01

    Full Text Available The study presents an outline of the effects in private law (including private international law of the non-recognition of a state or a change of territory. Specifically, it addresses the question of what measures can another state take, in the field of private law, in order to give effect to its policy of not recognizing a state or a territorial annexation, and, in parallel, what are the means available to private parties with links to the unrecognized state or territory. The study is structured in two parts, namely 1 the effects in private law of the non-recognition of a state; and 2 the effect in private law of the non-recognition of an annexation of territory. I will make specific references in particular to the situation in Transnistria and Crimea, as examples of the two issues being addressed. The study intends to be a guide of past and present state practice at the legislative and judicial level, as well as presenting the connections between instruments of public international law, such as Sanctions Resolutions of the UN Security Council, and normative instruments of private law, such as rules of civil procedure, which must adapt to the policy of non-recognition adopted by (or imposed on states. The study also presents specific examples of situations or administrative practices which create practical problems, and result from the existence of a non-recognized entity or change of territory: issues like air traffic coordination, postal traffic, the change in the official currency of a territory, questions of citizenship etc., the aim being to present the reader with a full picture of the issues and intricacies resulting from irregularities existing at the level of the international community of states.

  12. Pesticide Exposure and Neurodevelopmental Outcomes: Review of the Epidemiologic and Animal Studies

    Science.gov (United States)

    Burns, Carol J.; McIntosh, Laura J.; Mink, Pamela J.; Jurek, Anne M.; Li, Abby A.

    2013-01-01

    Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective

  13. Pesticide exposure and neurodevelopmental outcomes: review of the epidemiologic and animal studies.

    Science.gov (United States)

    Burns, Carol J; McIntosh, Laura J; Mink, Pamela J; Jurek, Anne M; Li, Abby A

    2013-01-01

    Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective

  14. Effectiveness comparison of partially executed t-way test suite based generated by existing strategies

    Science.gov (United States)

    Othman, Rozmie R.; Ahmad, Mohd Zamri Zahir; Ali, Mohd Shaiful Aziz Rashid; Zakaria, Hasneeza Liza; Rahman, Md. Mostafijur

    2015-05-01

    Consuming 40 to 50 percent of software development cost, software testing is one of the most resource consuming activities in software development lifecycle. To ensure an acceptable level of quality and reliability of a typical software product, it is desirable to test every possible combination of input data under various configurations. Due to combinatorial explosion problem, considering all exhaustive testing is practically impossible. Resource constraints, costing factors as well as strict time-to-market deadlines are amongst the main factors that inhibit such consideration. Earlier work suggests that sampling strategy (i.e. based on t-way parameter interaction or called as t-way testing) can be effective to reduce number of test cases without effecting the fault detection capability. However, for a very large system, even t-way strategy will produce a large test suite that need to be executed. In the end, only part of the planned test suite can be executed in order to meet the aforementioned constraints. Here, there is a need for test engineers to measure the effectiveness of partially executed test suite in order for them to assess the risk they have to take. Motivated by the abovementioned problem, this paper presents the effectiveness comparison of partially executed t-way test suite generated by existing strategies using tuples coverage method. Here, test engineers can predict the effectiveness of the testing process if only part of the original test cases is executed.

  15. [Neurodevelopmental theories of schizophrenia--preclinical studies].

    Science.gov (United States)

    Lehner, Małgorzata; Taracha, Ewa; Wisłowska, Aleksandra; Zienowicz, Małgorzata; Maciejak, Piotr; Skórzewska, Anna; Płaźnik, Adam

    2003-01-01

    Schizophrenia is a complex disorder of unknown origin, characterised by abnormalities in the realms of perception, thinking and the experience of emotions that onset is restricted to young adulthood. Many techniques that range from neuropathology to neuroimaging identified subtle brain abnormalities particularly in frontal, temporal cortex, hippocampus, basal ganglia and cerebellum. Neurodevelopmental models of schizophrenia test hypotheses that this disease is caused by a defect in cerebral development which results in altered neural connectivity, brain neurochemistry and aberrant behaviour observed in adult life. Recent evidence indicates that neonatal hippocampal damage may affect prefrontal neuronal integrity. The developmental lesion model appears to have predictive validity because treatment with antipsychotic drugs normalises some abnormal behaviour changes. Therefore it will be a useful paradigm in the work on new therapies and in providing new insights about pathophysiology and etiology of schizophrenia.

  16. Sleep in children with neurodevelopmental disabilities.

    Science.gov (United States)

    Angriman, Marco; Caravale, Barbara; Novelli, Luana; Ferri, Raffaele; Bruni, Oliviero

    2015-06-01

    This review describes recent research in pediatric sleep disorders associated with neurodevelopmental disabilities (NDDs) and their treatment. NDDs affect more than 2% of the general population and represent more than 35% of the total cases of children referred to a neuropsychiatric center for sleep problems. Specific clinical and therapeutic aspects of sleep disorders associated with Down syndrome, Fragile X syndrome, Prader-Willi syndrome, Angelman syndrome, Rett syndrome, Smith-Magenis syndrome, cerebral palsy, and autism spectrum disorders are described. Furthermore, the drugs commonly used for sleep disorders in children with NDDs are described. The review clearly highlighted that children with NDDs are often affected by sleep disorders that require appropriate clinical and therapeutic approach to improve quality of life in both patients and families. Georg Thieme Verlag KG Stuttgart · New York.

  17. Neurodevelopmental processes and psychological functioning in autism.

    Science.gov (United States)

    Gillberg, C

    1999-01-01

    Autism is a developmental disorder with variable severity, occurring at all levels of cognitive ability and having a number of slightly different clinical presentations. It is associated with neuropsychological deficits that occur in other conditions also, but its pattern may be specific to autism. Genetic and environmental early insults to brain development are etiological determinants of the disorder. Brain circuitries important for social, communicative, and integrational purposes have been suggested to be dysfunctional in autism. There could be at least two different pathways to autism, one connected with primary temporofrontal dysfunction (and late prenatal-early postnatal origins) and another linked to primary brain-stem dysfunction (and early prenatal origins). Further study of neurodevelopmental and neuropsychological processes in autism will help elucidate not only the pathological mechanisms involved in the specific syndromes but also the underpinnings of normal brain development.

  18. Complex Neurodevelopmental Disorders And Their Genetic Etiologies

    Directory of Open Access Journals (Sweden)

    Amna Batool

    2015-08-01

    Full Text Available Complex Neurodevelopmental disorders NDDs exhibit complex etiological and genetic features and the mutations have a fundamental role in this complexity including common polymorphisms and rare variations in a single gene or cluster of genes. The analysis of complex NDDs have shown that the genetics has the major role in causation of such complex diseases. Interestingly both mutations and polymorphisms are involved occurring in a single gene or clusters of genes. Likewise a single gene variation may also be involved in multiple neurological disorders making the diagnosis of neurological diseases more difficult. Many candidate genes and chromosomal regions have been identified that are widely involved in neurological symptoms which necessitates the genotypic approach for describing the phenotype.

  19. Neurobiology of depression: A neurodevelopmental approach.

    Science.gov (United States)

    Lima-Ojeda, Juan M; Rupprecht, Rainer; Baghai, Thomas C

    2017-03-03

    The main aims of this paper are to review and evaluate the neurobiology of the depressive syndrome from a neurodevelopmental perspective. An English language literature search was performed using PubMed. Depression is a complex syndrome that involves anatomical and functional changes that have an early origin in brain development. In subjects with genetic risk for depression, early stress factors are able to mediate not only the genetic risk but also gene expression. There is evidence that endocrine and immune interactions have an important impact on monoamine function and that the altered monoamine signalling observed in the depressive syndrome has a neuro-endocrino-immunological origin early in the development. Neurodevelopment is a key aspect to understand the whole neurobiology of depression.

  20. The positive effect of targeted marketing on an existing uterine fibroid embolization practice.

    Science.gov (United States)

    Chrisman, Howard B; Basu, Pat Auveek; Omary, Reed A

    2006-03-01

    Although uterine fibroid embolization is an effective treatment option for symptomatic women, it is unclear what methods can be used to expand referrals in an already established practice. The authors tested the hypothesis that an advertising strategy focused on a defined target market can expand an existing uterine fibroid embolization practice. A market-driven planning sequence was employed. This included a determination of goals, an examination of current competition, determination of target market based on local environment and previous consumer use, pretest of product sample, and implementation of advertisement. Based on the analysis the authors determined that the target audience was professional black women aged 35 to 45. A specific weekly magazine was selected due to readership demographics. An advertisement was run for 8 consecutive weeks. The authors prospectively tracked patient inquiries, clinic visits, cases performed, and revenues generated for 3 months following the initial advertisement. All patients were seen in a fully staffed, preexisting fibroid clinic located within an urban, university-based academic practice performing 250 uterine fibroid embolizations annually. Ninety calls were received directly related to the advertisement. There were 35 clinic visits, which resulted in 17 uterine fibroid embolizations and 52 total MR imaging procedures. Eighteen patients were not considered candidates based on established protocols. The 17 extra cases performed over 3 months represented a 27% increase in case volume. Total professional cash collections for these cases (including MR imaging) were 58,317 US dollars. The cost of advertising was 8,000 US dollars. As a result of existing infrastructure, no additional costs were necessary. This resulted in a net revenue gain 50,317 US dollars and a nonannualized rate of return of approximately 625%. As Interventional Radiologists look to develop and expand existing practices, traditional marketing tools such as

  1. Regulative Conditions of Existence of Doppler Effect Using Green Function Formalism

    Directory of Open Access Journals (Sweden)

    R El Bahi

    2017-06-01

    Full Text Available The Doppler shift of the near and far Waves due to the electromagnetic source in motion is investigated. Using the decomposition of Green’s function for the wave in the case of classical oscillating electron motion, it is found that there are some regulative conditions of the phenomena. The present theory proves that the shift is undefined in the adjacent area. Actually, the spectrum of the radiation field in the adjacent area is ambiguous. The current theory establishes a regular Doppler effect in the distant area. Bearing in mind that the propagator coupled with the electric field takes a shifted frequency. Once, the relationship between the far-field frequency, the oscillating dynamic source have been established, the spectrum exists and can be analyzed.

  2. Brain Injury and Neurodevelopmental Outcome in Congenital Heart Disease: A Systematic Review.

    Science.gov (United States)

    Mebius, Mirthe J; Kooi, Elisabeth M W; Bilardo, Catherina M; Bos, Arend F

    2017-07-01

    Brain injury during prenatal and preoperative postnatal life might play a major role in neurodevelopmental impairment in infants with congenital heart disease (CHD) who require corrective or palliative surgery during infancy. A systematic review of cerebral findings during this period in relation to neurodevelopmental outcome (NDO), however, is lacking. To assess the association between prenatal and postnatal preoperative cerebral findings and NDO in infants with CHD who require corrective or palliative surgery during infancy. PubMed, Embase, reference lists. We conducted 3 different searches for English literature between 2000 and 2016; 1 for prenatal cerebral findings, 1 for postnatal preoperative cerebral findings, and 1 for the association between brain injury and NDO. Two reviewers independently screened sources and extracted data on cerebral findings and neurodevelopmental outcome. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Abnormal cerebral findings are common during the prenatal and postnatal preoperative periods. Prenatally, a delay of cerebral development was most common; postnatally, white matter injury, periventricular leukomalacia, and stroke were frequently observed. Abnormal Doppler measurements, brain immaturity, cerebral oxygenation, and abnormal EEG or amplitude-integrated EEG were all associated with NDO. Observational studies, different types of CHD with different pathophysiological effects, and different reference values. Prenatal and postnatal preoperative abnormal cerebral findings might play an important role in neurodevelopmental impairment in infants with CHD. Increased awareness of the vulnerability of the young developing brain of an infant with CHD among caregivers is essential. Copyright © 2017 by the American Academy of Pediatrics.

  3. Pre-existent expectancy effects in the relationship between caffeine and performance.

    Science.gov (United States)

    Elliman, Nicola A; Ash, Jennifer; Green, Michael W

    2010-10-01

    The present study investigated the impact of pre-existent expectancy regarding the effects of the caffeine load of a drink and the perception of the caffeine content on subjective mood and vigilance performance. Caffeine deprived participants (N=25) were tested in four conditions (within subjects design), using a 2×2 design, with caffeine load and information regarding the caffeine content of the drink. In two sessions, they were given caffeinated coffee and in two were given decaffeinated coffee. Within these two conditions, on one occasion they were given accurate information about the drink and on the other they were given inaccurate information about the drink. Mood and vigilance performance were assessed post ingestion. Caffeine was found to enhance performance, but only when participants were accurately told they were receiving it. When decaffeinated coffee was given, performance was poorer, irrespective of expectancy. However, when caffeine was given, but participants were told it was decaffeinated coffee, performance was as poor as when no caffeine had been administered. There were no easily interpretable effects on mood. The pharmacological effects of caffeine appear to act synergistically with expectancy.

  4. Evaluating the effects that existing instruction on responsible conduct of research has on ethical decision making.

    Science.gov (United States)

    Antes, Alison L; Wang, Xiaoqian; Mumford, Michael D; Brown, Ryan P; Connelly, Shane; Devenport, Lynn D

    2010-03-01

    To examine the effects that existing courses on the responsible conduct of research (RCR) have on ethical decision making by assessing the ethicality of decisions made in response to ethical problems and the underlying processes involved in ethical decision making. These processes included how an individual thinks through ethical problems (i.e., meta-cognitive reasoning strategies) and the emphasis placed on social dimensions of ethical problems (i.e., social-behavioral responses). In 2005-2007, recruitment announcements were made, stating that a nationwide, online study was being conducted to examine the impact of RCR instruction on the ethical decision making of scientists. Recruitment yielded contacts with over 200 RCR faculty at 21 research universities and medical schools; 40 (20%) RCR instructors enrolled their courses in the current study. From those courses, 173 participants completed an ethical decision-making measure. A mixed pattern of effects emerged. The ethicality of decisions did not improve as a result of RCR instruction and even decreased for decisions pertaining to business aspects of research, such as contract bidding. Course participants improved on some meta-cognitive reasoning strategies, such as awareness of the situation and consideration of personal motivations, but declined for seeking help and considering others' perspectives. Participants also increased their endorsement of detrimental social-behavioral responses, such as deception, retaliation, and avoidance of personal responsibility. These findings indicated that RCR instruction may not be as effective as intended and, in fact, may even be harmful. Harmful effects might result if instruction leads students to overstress avoidance of ethical problems, be overconfident in their ability to handle ethical problems, or overemphasize their ethical nature. Future research must examine these and other possible obstacles to effective RCR instruction.

  5. Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?

    Science.gov (United States)

    Bruining, Hilgo; Passtoors, Laurien; Goriounova, Natalia; Jansen, Floor; Hakvoort, Britt; de Jonge, Maretha; Poil, Simon-Shlomo

    2015-08-01

    The diuretic agent bumetanide has recently been put forward as a novel, promising treatment of behavioral symptoms in autism spectrum disorder (ASD) and related conditions. Bumetanide can decrease neuronal chloride concentrations and may thereby reinstate γ-aminobutyric acid (GABA)-ergic inhibition in patients with neurodevelopmental disorders. However, strategies to select appropriate candidates for bumetanide treatment are lacking. We hypothesized that a paradoxical response to GABA-enforcing agents such as benzodiazepines may predict the efficacy of bumetanide treatment in neurodevelopmental disorders. We describe a case of a 10-year-old girl with ASD, epilepsy, cortical dysplasia, and a 15q11.2 duplication who had exhibited marked behavioral arousal after previous treatment with clobazam, a benzodiazepine. We hypothesized that this response indicated the presence of depolarizing excitatory GABA and started bumetanide treatment with monitoring of behavior, cognition, and EEG. The treatment resulted in a marked clinical improvement in sensory behaviors, rigidity, and memory performance, which was substantiated by questionnaires and cognitive assessments. At baseline, the girl's EEG showed a depression in absolute α power, an electrographic sign previously related to ASD, which was normalized with bumetanide treatment. The effects of bumetanide on cognition and EEG seemed to mirror the "nonparadoxical" responses to benzodiazepines in healthy subjects. In addition, temporal lobe epilepsy and cortical dysplasia have both been linked to disturbed chloride homeostasis and seem to support our assumption that the observed paradoxical response was due to GABA-mediated excitation. This case highlights that a paradoxical behavioral response to GABA-enforcing drugs may constitute a framework for targeted treatment with bumetanide. Copyright © 2015 by the American Academy of Pediatrics.

  6. Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum.

    Science.gov (United States)

    Fejzo, Marlena S; Magtira, Aromalyn; Schoenberg, Frederic Paik; Macgibbon, Kimber; Mullin, Patrick M

    2015-06-01

    The purpose of this study is to determine the frequency of emotional, behavioral, and learning disorders in children exposed in utero to hyperemesis gravidarum (HG) and to identify prognostic factors for these disorders. Neurodevelopmental outcomes of 312 children from 203 mothers with HG were compared to neurodevelopmental outcomes from 169 children from 89 unaffected mothers. Then the clinical profiles of patients with HG and a normal child outcome were compared to the clinical profiles of patients with HG and a child with neurodevelopmental delay to identify prognostic factors. Binary responses were analyzed using either a Chi-square or Fisher Exact test and continuous responses were analyzed using a t-test. Children exposed in utero to HG have a 3.28-fold increase in odds of a neurodevelopmental diagnosis including attention disorders, learning delay, sensory disorders, and speech and language delay (Ppregnancies, only early onset of symptoms (prior to 5 weeks gestation) was significantly linked to neurodevelopmental delay. We found no evidence for increased risk of 13 emotional, behavioral, and learning disorders, including autism, intellectual impairment, and obsessive-compulsive disorder. However, the study was not sufficiently powered to detect rare conditions. Medications, treatments, and preterm birth were not associated with an increased risk for neurodevelopmental delay. Women with HG are at a significantly increased risk of having a child with neurodevelopmental delay. Common antiemetic treatments were not linked to neurodevelopmental delay, but early symptoms may play a role. There is an urgent need to address whether aggressive treatment that includes vitamin and nutrient supplementation in women with early symptoms of severe nausea of pregnancy decreases the risk of neurodevelopmental delay. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. The mere exposure effect for consumer products as a consequence of existing familiarity and controlled exposure.

    Science.gov (United States)

    Hekkert, Paul; Thurgood, Clementine; Whitfield, T W Allan

    2013-10-01

    The finding that repeated exposure to a stimulus enhances attitudes directed towards it is a well-established phenomenon. Despite this, the effects of exposure to products are difficult to determine given that they could have previously been exposed to participants any number of times. Furthermore, factors other than simple repeated exposure can influence affective evaluations for stimuli that are meaningful. In our first study, we examined the influence of existing familiarity with common objects and showed that the attractiveness of shapes representing common objects increases with their rated commonness. In our second study, we eliminated the effects of prior exposure by creating fictitious yet plausible products; thus, exposure frequency was under complete experimental control. We also manipulated the attention to be drawn to the products' designs by placing them in contexts where their visual appearance was stressed to be important versus contexts in which it was indicated that little attention had been paid to their design. Following mere exposure, attractiveness ratings increased linearly with exposure frequency, with the slope of the function being steeper for stimuli presented in an inconspicuous context-indicating that individuals engage in more deliberate processing of the stimuli when attention is drawn to their visual appearance. © 2013 Elsevier B.V. All rights reserved.

  8. The mechanical effect of the existing cement mantle on the in-cement femoral revision.

    LENUS (Irish Health Repository)

    Keeling, Parnell

    2012-08-01

    Cement-in-cement revision hip arthroplasty is an increasingly popular technique to replace a loose femoral stem which retains much of the original cement mantle. However, some concern exists regarding the retention of the existing fatigued and aged cement in such cement-in-cement revisions. This study investigates whether leaving an existing fatigued and aged cement mantle degrades the mechanical performance of a cement-in-cement revision construct.

  9. 16 Investigating the effects of under-triage by existing major incident triage tools.

    Science.gov (United States)

    Vassallo, James; Smith, Jason

    2017-12-01

    Triage, the process of prioritising patients on the basis of clinical acuity, is a key principle in the effective management of a major incident. The overall effectiveness of the triage process is not only a balance between identifying those who need or don't need a life-saving intervention, but also those who are under or over-triaged as either incorrectly needing/not needing intervention. The primary aim of this study was to describe the implications of under-triage using existing major incident triage tools, including the 2013 National Ambulance Resilience Unit (NARU) Sieve. The secondary aim was to describe the safety profile of the Modified Physiological Triage Tool (MPTT) in comparison to other triage tools, and to report mortality and identification of serious injury (AIS>3) in discrete AIS body regions. A retrospective database review was undertaken using the UK Trauma Audit Research Network for all adult patients (>18 years) between 2006-2014. Patients were defined as Priority One using a previously published list. Using first recorded hospital physiology, patients were categorised by the MPTT, NARU Sieve and existing Triage Sieve. Data are presented as number (%) and median (IQR) as appropriate. Categorical data were analysed using a Chi Square test and continuous data with a Mann-Whitney U test. During the study period, 2 18 985 adult patients were included with 24 791 (19.5%) identified as Priority One. 70% were male, aged 51 years [33-71], ISS 16 [9-25] with road traffic collision the most common mechanism (34%). The MPTT demonstrated the lowest rate of under-triage (42.4%, ptools are used in the context of a major trauma population. The MPTT misses fewer severely injured patients, with fewer LSIs necessary in the under-triaged population. We suggest that the MPTT should be considered as an alternative to existing major incident triage tools.emermed;34/12/A871-a/T1F2T1Table 1Frequency of interventions performed in the priority one cohort and

  10. Trampling on maritime Antarctica: can soil ecosystems be effectively protected through existing codes of conduct?

    Directory of Open Access Journals (Sweden)

    Pablo Tejedo

    2012-12-01

    Full Text Available Soil trampling is one of the most obvious direct negative human impacts in Antarctica. Through a range of experiments and field studies based on quantitative physical (soil penetration resistance and biological (collembolan abundance indicators, we evaluate the current codes of conduct relating to the protection of Antarctic soils from the consequences of pedestrian impacts. These guidelines include using, where available, established paths that cross vegetation-free soils. However, the effectiveness of this strategy is highly dependent on context. Limited intensity use—below 100 foot passes per year—produces small changes at the soil surface that can recover relatively rapidly, suggesting that the dispersal of activity across wider corridors may be the most appropriate option. However, for paths with a higher use level and those located in steep-sloped sites, it is desirable to define a single track, following stony or bouldery surfaces wherever possible, to keep the disturbed area to a minimum. It is clear that both environmental conditions and expected use levels must be taken into account in determining when and where it is more appropriate to concentrate or disperse human activities. Even though they may have performed satisfactorily to date, the increasing pressure in terms of numbers of visits for certain sites may make it necessary to revise existing codes of conduct.

  11. The Effect Of The Original Acquisition Of Ownership Of Immovable Property On Existing Limited Real Rights

    Directory of Open Access Journals (Sweden)

    Gerrit Pienaar

    2015-12-01

    Full Text Available It is an accepted principle in South African law that movable property acquired in an original way (by operation of law is not burdened by any limited real rights, as previous limited real rights are extinguished on the vesting of ownership (mobilia non habent sequelam. It is assumed by some South African writers that the same principles are applicable to the original acquisition of immovable property and that all existing limited real rights fall away on original acquisition of ownership. In this article the nature of limited real rights to immovable property is examined, and the notion that ownership is the "mother" right on which all limited real rights are based is scrutinised critically. The nature and establishment of limited real rights are used to distinguish between the essence and effect of limited real rights in the case of immovable property. The recognition of limited real rights as constitutional property is used as a further argument that limited real rights cannot be extinguished automatically by the original acquisition of immovable property, as such common law or statutory measures will constitute an arbitrary deprivation of property in terms of section 25 of the Constitution. The statutory provisions regarding limited real rights in the case of prescription and expropriation are then analysed as an indication that it is not a general principle that limited real rights are extinguished automatically on the original acquisition of ownership of immovable property.

  12. Effectiveness evaluation of existing noise controls in a deep shaft underground mine.

    Science.gov (United States)

    Lutz, Eric A; Reed, Rustin J; Turner, Dylan; Littau, Sally R; Lee, Vivien; Hu, Chengcheng

    2015-01-01

    Noise exposures and hearing loss in the mining industry continue to be a major problem, despite advances in noise control technologies. This study evaluated the effectiveness of engineering, administrative, and personal noise controls using both traditional and in-ear dosimetry by job task, work shift, and five types of earplug. The noise exposures of 22 miners performing deep shaft-sinking tasks were evaluated during 56 rotating shifts in an underground mine. Miners were earplug-insertion trained, earplug fit-tested, and monitored utilizing traditional and in-ear dosimetry. The mean TWA8 noise exposure via traditional dosimetry was 90.1 ± 8.2 dBA, while the mean in-ear TWA8 was 79.6 ± 13.8 dBA. The latter was significantly lower (p earplug used. Reflective of occupational hearing loss rate trends across the mining industry, this study found that, despite existing engineering and administrative controls, noise exposure levels exceeded regulatory limits, while the addition of personal hearing protection limited excessive exposures.

  13. The effect of repeated exposure to ethanol on pre-existing fear memories in rats.

    Science.gov (United States)

    Quiñones-Laracuente, Kelvin; Hernández-Rodríguez, Marán Y; Bravo-Rivera, Christian; Melendez, Roberto I; Quirk, Gregory J

    2015-10-01

    There is a high degree of comorbidity between alcohol use disorder and post-traumatic stress disorder (PTSD), but little is known about the interactions of ethanol with traumatic memories. Using auditory fear conditioning in rats, we asked if repeated exposure to ethanol could modify the retrieval of fear memories acquired prior to ethanol exposure. Following auditory fear conditioning, Sprague-Dawley rats were given daily injections of ethanol (1.5 g/kg) or saline over 5 days. Two days later, they were given 20 trials of extinction training and then tested for extinction memory the following day. In a separate experiment, conditioned rats were given repeated ethanol injections and processed for c-Fos immunohistochemistry following a fear retrieval session. Two days following the cessation of ethanol, the magnitude of conditioned fear responses (freezing and suppression of bar pressing) was significantly increased. This increase persisted the following day. Waiting 10 days following cessation of ethanol eliminated the effect on fear retrieval. In rats conditioned with low shock levels, repeated exposure to ethanol converted a sub-threshold fear memory into a supra-threshold fear memory. It also increased c-Fos expression in the prelimbic prefrontal cortex, paraventricular thalamus, and the central and basolateral nuclei of the amygdala, areas implicated in the retrieval of fear memories. These results suggest that repeated exposure to ethanol may exacerbate pre-existing traumatic memories.

  14. Potential surface alteration effects of laser-assisted periodontal surgery on existing dental restorations.

    Science.gov (United States)

    Kilinc, Evren; Rothrock, James; Migliorati, Erica; Drukteinis, Saulius; Roshkind, David M; Bradley, Paul

    2012-05-01

    Laser-assisted gingivectomies are performed in proximity to teeth, existing restorations, and implants. In case of accidental exposures, a detrimental surface defect may cause failure. Surface interactions should be evaluated for safety margin determination of certain laser-material combinations. The purpose of this in vitro study was to assess the microscopic and visible effects of CO2, Nd:YAG, and 810-nm diode laser irradiations on various dental materials and tooth tissue. Study samples were fabricated (10 x 7.5 mm irradiation surface area, 1 mm thickness) from eight material groups (amalgam, base metal, gold, palladium-silver, composite, ceramic, titanium, and extracted tooth slices). Laser irradiations were performed with CO2, Nd:YAG, and 810-nm diode lasers using the manufacturer's recommended settings for gingivectomy at a 45-degree angle for 30 seconds. Irradiated surfaces were evaluated under SEM at 200x and 1,000x magnifications. Standardized photographs were obtained using a camera mount system (10x high-definition macro lens). The SEM images and photographs were correlated to determine surface interactions. Nd:YAG detrimentally affected all metallic materials and tooth structures. CO2 altered amalgam, gold, and palladium-silver slightly, whereas composite, ceramic, and tooth surfaces were detrimentally altered. The 810-nm diode altered amalgam, gold, titanium, palladium-silver, and composite but only gold and palladium-silver surfaces were barely traceable. Within the limitations of this in vitro study, surface effects were all instant; therefore, even a short accidental exposure may be destructive in some laser-material combinations. During gingivectomies, CO2 near tooth-colored restorations and Nd:YAG near metallic restorations and implants should be used carefully. The 810-nm diode was found to be safer due to its reversible alterations in only some materials. Further in vivo studies are necessary to clinically apply the outcomes of this study.

  15. Cross Talk: The Microbiota and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    John R. Kelly

    2017-09-01

    Full Text Available Humans evolved within a microbial ecosystem resulting in an interlinked physiology. The gut microbiota can signal to the brain via the immune system, the vagus nerve or other host-microbe interactions facilitated by gut hormones, regulation of tryptophan metabolism and microbial metabolites such as short chain fatty acids (SCFA, to influence brain development, function and behavior. Emerging evidence suggests that the gut microbiota may play a role in shaping cognitive networks encompassing emotional and social domains in neurodevelopmental disorders. Drawing upon pre-clinical and clinical evidence, we review the potential role of the gut microbiota in the origins and development of social and emotional domains related to Autism spectrum disorders (ASD and schizophrenia. Small preliminary clinical studies have demonstrated gut microbiota alterations in both ASD and schizophrenia compared to healthy controls. However, we await the further development of mechanistic insights, together with large scale longitudinal clinical trials, that encompass a systems level dimensional approach, to investigate whether promising pre-clinical and initial clinical findings lead to clinical relevance.

  16. Which neurodevelopmental disorders get researched and why?

    Science.gov (United States)

    Bishop, Dorothy V M

    2010-11-30

    There are substantial differences in the amount of research concerned with different disorders. This paper considers why. Bibliographic searches were conducted to identify publications (1985-2009) concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairment, Attention deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome, Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome, Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams syndrome, XXX and XYY. A publication index reflecting N publications relative to prevalence was derived. The publication index was higher for rare than common conditions. However, this was partly explained by the tendency for rare disorders to be more severe. Although research activity is predictable from severity and prevalence, there are exceptions. Low rates of research, and relatively low levels of NIH funding, characterise conditions that are the domain of a single discipline with limited research resources. Growth in research is not explained by severity, and was exceptionally steep for autism and ADHD.

  17. Cross Talk: The Microbiota and Neurodevelopmental Disorders

    Science.gov (United States)

    Kelly, John R.; Minuto, Chiara; Cryan, John F.; Clarke, Gerard; Dinan, Timothy G.

    2017-01-01

    Humans evolved within a microbial ecosystem resulting in an interlinked physiology. The gut microbiota can signal to the brain via the immune system, the vagus nerve or other host-microbe interactions facilitated by gut hormones, regulation of tryptophan metabolism and microbial metabolites such as short chain fatty acids (SCFA), to influence brain development, function and behavior. Emerging evidence suggests that the gut microbiota may play a role in shaping cognitive networks encompassing emotional and social domains in neurodevelopmental disorders. Drawing upon pre-clinical and clinical evidence, we review the potential role of the gut microbiota in the origins and development of social and emotional domains related to Autism spectrum disorders (ASD) and schizophrenia. Small preliminary clinical studies have demonstrated gut microbiota alterations in both ASD and schizophrenia compared to healthy controls. However, we await the further development of mechanistic insights, together with large scale longitudinal clinical trials, that encompass a systems level dimensional approach, to investigate whether promising pre-clinical and initial clinical findings lead to clinical relevance. PMID:28966571

  18. Which neurodevelopmental disorders get researched and why?

    Directory of Open Access Journals (Sweden)

    Dorothy V M Bishop

    2010-11-01

    Full Text Available There are substantial differences in the amount of research concerned with different disorders. This paper considers why.Bibliographic searches were conducted to identify publications (1985-2009 concerned with 35 neurodevelopmental disorders: Developmental dyslexia, Developmental dyscalculia, Developmental coordination disorder, Speech sound disorder, Specific language impairment, Attention deficit hyperactivity disorder, Autistic spectrum disorder, Tourette syndrome, Intellectual disability, Angelman syndrome, Cerebral palsy, Cornelia de Lange syndrome, Cri du chat syndrome, Down syndrome, Duchenne muscular dystrophy, Fetal alcohol syndrome, Fragile X syndrome, Galactosaemia, Klinefelter syndrome, Lesch-Nyhan syndrome, Lowe syndrome, Marfan syndrome, Neurofibromatosis type 1, Noonan syndrome, Phenylketonuria, Prader-Willi syndrome, Rett syndrome, Rubinstein-Taybi syndrome, Trisomy 18, Tuberous sclerosis, Turner syndrome, Velocardiofacial syndrome, Williams syndrome, XXX and XYY. A publication index reflecting N publications relative to prevalence was derived.The publication index was higher for rare than common conditions. However, this was partly explained by the tendency for rare disorders to be more severe.Although research activity is predictable from severity and prevalence, there are exceptions. Low rates of research, and relatively low levels of NIH funding, characterise conditions that are the domain of a single discipline with limited research resources. Growth in research is not explained by severity, and was exceptionally steep for autism and ADHD.

  19. Models of Neurodevelopmental Abnormalities in Schizophrenia

    Science.gov (United States)

    Powell, Susan B.

    2013-01-01

    The neurodevelopmental hypothesis of schizophrenia asserts that the underlying pathology of schizophrenia has its roots in brain development and that these brain abnormalities do not manifest themselves until adolescence or early adulthood. Animal models based on developmental manipulations have provided insight into the vulnerability of the developing fetus and the importance of the early environment for normal maturation. These models have provided a wide range of validated approaches to answer questions regarding environmental influences on both neural and behavioral development. In an effort to better understand the developmental hypothesis of schizophrenia, animal models have been developed, which seek to model the etiology and/or the pathophysiology of schizophrenia or specific behaviors associated with the disease. Developmental models specific to schizophrenia have focused on epidemiological risk factors (e.g., prenatal viral insult, birth complications) or more heuristic models aimed at understanding the developmental neuropathology of the disease (e.g., ventral hippocampal lesions). The combined approach of behavioral and neuroanatomical evaluation of these models strengthens their utility in improving our understanding of the pathophysiology of schizophrenia and developing new treatment strategies. PMID:21312409

  20. Neurodevelopmental Outcomes After Neonatal Surgery for Major Noncardiac Anomalies

    NARCIS (Netherlands)

    Stolwijk, Lisanne J.; Lemmers, P. M A; Harmsen, Marissa; Groenendaal, Floris; De Vries, Linda S.; Van Der Zee, David C.; Benders, Manon J N; Van Herwaarden-Lindeboom, M. Y A

    2016-01-01

    CONTEXT: Increasing concerns have been raised about the incidence of neurodevelopmental delay in children with noncardiac congenital anomalies (NCCA) requiring neonatal surgery. OBJECTIVE: This study aimed to determine the incidence and potential risk factors for developmental delay after neonatal

  1. Effect of the Existence of Brownfields on Selected Item Expenditure of Municipal Budgets

    Directory of Open Access Journals (Sweden)

    Endel Stanislav

    2017-06-01

    Full Text Available The existence of brownfields in an area results in a number of problems. Among others, economic problems are often mentioned. They are mainly connected with negative influence on urban economics, i.e. the total cost of construction and operation of the city. These increased costs are then naturally reflected in the budgets of municipalities burdened by the existence of brownfields. This paper presents the individual items of municipal budgets, which can be influenced by the existence of brownfields, and then examines on a practical example of six Czech towns whether any functional dependence can be found between these items and a number of brownfields in the municipalities.

  2. The Neurodevelopmental Impact of Neonatal Morphine Administration

    Directory of Open Access Journals (Sweden)

    Stephanie Attarian

    2014-04-01

    Full Text Available Medical management of newborn infants often necessitates recurrent painful procedures, which may alter nociceptive pathways during a critical developmental period and adversely effect neuropsychological outcomes. To mitigate the effects of repeated painful stimuli, opioid administration for peri-procedural analgesia and ICU (intensive care unit sedation is common in the NICU (neonatal intensive care unit. A growing body of basic and animal evidence suggests potential long-term harm associated with neonatal opioid therapy. Morphine increases apoptosis in human microglial cells, and animal studies demonstrate long-term changes in behavior, brain function, and spatial recognition memory following morphine exposure. This comprehensive review examines existing preclinical and clinical evidence on the long-term impacts of neonatal pain and opioid therapy.

  3. Existence and Ulam stabilities for Hadamard fractional integral equations with random effects

    Directory of Open Access Journals (Sweden)

    Said Abbas

    2016-01-01

    Full Text Available This article concerns the existence and Ulam stabilities for a class of random integral equations via Hadamard's fractional integral. Our main tools is a random fixed point theorem with stochastic domain.

  4. Insights on Extent of Effectiveness, Trend, and Gap in Existing Frameworks for e-Procurement System

    National Research Council Canada - National Science Library

    N Madhusudan; L Manjunatha Rao

    2016-01-01

    .... However, this trend was not observed much on the e-Procurement system, where the existing users still place the purchase order using conventional web-based approach that cannot address various...

  5. The Effects of Forest Disturbance on Macroinvertebrates in Western Oregon Headwater Streams - Patterns in Existing Databases

    Science.gov (United States)

    Herlihy, A. T.; Li, J.; Gerth, B.; Banks, J.

    2003-12-01

    As part of a research project investigating the effects of forest harvest practices on stream macroinvertebrates, we compiled existing data for Western Oregon headwater forest streams. The compiled database consists of 168 sites with watershed areas less than 10 square km that had measurements of stream macroinvertebrates, fish, physical habitat, water chemistry, and watershed land cover. The source of the data is from surveys conducted for EPA's EMAP program, the state of Oregon's Salmon Plan monitoring, and our own sampling efforts between 1994 and 2000. Almost all sites in the database were selected using the randomized EMAP survey design so they constitute a representative sample of all streams in this population. The streams in our dataset typically had mean wetted widths of 1-5 m, mean thalweg depths of 8-34 cm, and channel slopes of 1-15%. Watersheds for these sites were delineated and data on forest condition and logging history were clipped from available GIS layers. There were 189 macroinvertebrate taxa at the 168 sites with richness at individual sites ranging from 7 to 71 taxa. Ordination of the macroinvertebrate assemblages using NMS resulted in a 3 dimensional solution which accounted for 78% of the variation in the similarity among sites and demonstrated clear patterns in taxonomic composition with Baetis, Epeorus and Chironominae having the highest correlations with the ordination axes. Axes 1 and 2 each explained about 30% of the variation and were strongly correlated with substrate size, site slope and elevation. The third axis explained 17% of the variation and was correlated most strongly with watershed indices of forest logging history.

  6. Mevalonate Cascade and Neurodevelopmental and Neurodegenerative Diseases: Future Targets for Therapeutic Application.

    Science.gov (United States)

    Jiao, Xiaodan; Ashtari, Niloufar; Rahimi-Balaei, Maryam; Chen, Qi Min; Badbezanchi, Ilnaz; Shojaei, Shahla; Marzban, Adel; Mirzaei, Nima; Chung, Seunghyuk; Guan, Teng; Li, Jiasi; Vriend, Jerry; Mehr, Shahram Ejtemaei; Kong, Jiming; Marzban, Hassan

    2017-01-01

    The mevalonate cascade is a key metabolic pathway that regulates a variety of cellular functions and is thereby implicated in the pathophysiology of most brain diseases, including neurodevelopmental and neurodegenerative disorders. Emerging lines of evidence suggest that statins and Rho GTPase inhibitors are efficacious and have advantageous properties in treatment of different pathologic conditions that are relevant to the central nervous system. Beyond the original role of statins in lowering cholesterol synthesis, they have anti-inflammatory, antioxidant and modulatory effects on signaling pathways. Additionally, Rho GTPase inhibitors and statins share the mevalonate pathway as a common target of their therapeutic actions. In this review, we discuss potential mechanisms through which these drugs, via their role in the mevalonate pathway, exert their neuroprotective effects in neurodegenerative and neurodevelopmental disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Efficacy of Intensive Neurodevelopmental Treatment for Children With Developmental Delay, With or Without Cerebral Palsy

    OpenAIRE

    Lee, Kyoung-Hwan; Park, Jinwoo; Lee, Hojun; Nam, Kiyeun; Park, Tae June; Kim, Hee Jae; Kwon, Bumsun

    2017-01-01

    Objective To evaluate the effectiveness of intensive neurodevelopmental treatment (NDT) on gross motor function for the children having developmental delay (DD), with or without cerebral palsy (CP). Methods Forty-two children had intensive NDT three times weekly, 60 minutes a day, for 3 months, immediately followed by conventional NDT once or twice a week, 30 minutes a day, for another 3 months. We assessed Gross Motor Function Measure (GMFM) over three time points: before conventional NDT, b...

  8. Lack of evidence for neonatal misoprostol neurodevelopmental toxicity in C57BL6/J mice.

    Directory of Open Access Journals (Sweden)

    Claire M Koenig

    Full Text Available Misoprostol is a synthetic analogue of prostaglandin E1 that is administered to women at high doses to induce uterine contractions for early pregnancy termination and at low doses to aid in cervical priming during labor. Because of the known teratogenic effects of misoprostol when given during gestation and its effects on axonal growth in vitro, we examined misoprostol for its potential as a neurodevelopmental toxicant when administered to neonatal C57BL6/J mice. Mice were injected subcutaneously (s.c. with 0.4, 4 or 40 µg/kg misoprostol on postnatal day 7, the approximate developmental stage in mice of human birth, after which neonatal somatic growth, and sensory and motor system development were assessed. These doses were selected to span the range of human exposure used to induce labor. In addition, adult mice underwent a battery of behavioral tests relevant to neurodevelopmental disorders such as autism including tests for anxiety, stereotyped behaviors, social communication and interactions, and learning and memory. No significant effects of exposure were found for any measure of development or behavioral endpoints. In conclusion, the results of the present study in C57BL/6J mice do not provide support for neurodevelopmental toxicity after misoprostol administration approximating human doses and timed to coincide with the developmental stage of human birth.

  9. Genes, Gender, Environment, and Novel Functions of Estrogen Receptor Beta in the Susceptibility to Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Mukesh Varshney

    2017-02-01

    Full Text Available Many neurological disorders affect men and women differently regarding prevalence, progression, and severity. It is clear that many of these disorders may originate from defective signaling during fetal or perinatal brain development, which may affect males and females differently. Such sex-specific differences may originate from chromosomal or sex-hormone specific effects. This short review will focus on the estrogen receptor beta (ERβ signaling during perinatal brain development and put it in the context of sex-specific differences in neurodevelopmental disorders. We will discuss ERβ’s recent discovery in directing DNA de-methylation to specific sites, of which one such site may bear consequences for the susceptibility to the neurological reading disorder dyslexia. We will also discuss how dysregulations in sex-hormone signaling, like those evoked by endocrine disruptive chemicals, may affect this and other neurodevelopmental disorders in a sex-specific manner through ERβ.

  10. When existence is not futile: The influence of mortality salience on the longer-is-better effect.

    Science.gov (United States)

    McCabe, Simon; Spina, Melissa R; Arndt, Jamie

    2016-09-01

    This research examines how death reminders impact the valuation of objects of various ages. Building from the existence bias, the longer-is-better effect posits that which exists is good and that which has existed for longer is better. Integrating terror management theory, it was reasoned that mortality reminders fostering a motivation to at least symbolically transcend death would lead participants to evaluate older object more positively as they signal robustness of existence. Participants were reminded of death (vs. control) and evaluated new, 20-, or 100-year-old objects. Results indicated death reminders resulted in greater valuation of older objects. Findings are discussed with implications for terror management theory, the longer-is-better effect, ageism, materialism, and consumer behaviour. © 2016 The British Psychological Society.

  11. Neurodevelopmental problems and extremes in BMI

    Directory of Open Access Journals (Sweden)

    Nóra Kerekes

    2015-07-01

    Full Text Available Background. Over the last few decades, an increasing number of studies have suggested a connection between neurodevelopmental problems (NDPs and body mass index (BMI. Attention deficit/hyperactivity disorder (ADHD and autism spectrum disorders (ASD both seem to carry an increased risk for developing extreme BMI. However, the results are inconsistent, and there have been only a few studies of the general population of children.Aims. We had three aims with the present study: (1 to define the prevalence of extreme (low or high BMI in the group of children with ADHD and/or ASDs compared to the group of children without these NDPs; (2 to analyze whether extreme BMI is associated with the subdomains within the diagnostic categories of ADHD or ASD; and (3 to investigate the contribution of genetic and environmental factors to BMI in boys and girls at ages 9 and 12.Method. Parents of 9- or 12-year-old twins (n = 12,496 were interviewed using the Autism—Tics, ADHD and other Comorbidities (A-TAC inventory as part of the Child and Adolescent Twin Study in Sweden (CATSS. Univariate and multivariate generalized estimated equation models were used to analyze associations between extremes in BMI and NDPs.Results. ADHD screen-positive cases followed BMI distributions similar to those of children without ADHD or ASD. Significant association was found between ADHD and BMI only among 12-year-old girls, where the inattention subdomain of ADHD was significantly associated with the high extreme BMI. ASD scores were associated with both the low and the high extremes of BMI. Compared to children without ADHD or ASD, the prevalence of ASD screen-positive cases was three times greater in the high extreme BMI group and double as much in the low extreme BMI group. Stereotyped and repetitive behaviors were significantly associated with high extreme BMIs.Conclusion. Children with ASD, with or without coexisting ADHD, are more prone to have low or high extreme BMIs than

  12. Implant placement under existing removable dental prostheses and its effect on masticatory performance.

    Science.gov (United States)

    Wolfart, S; Wolf, K; Brunzel, S; Wolfart, M; Caliebe, A; Kern, M

    2016-12-01

    The aim of this within-subject study was to evaluate the outcome with implant-tooth-supported removable partial dental prostheses (RPDP group) and implant-supported removable complete dental prostheses (edentulous group) in terms of masticatory performance and self-assessment. Thirty patients participated in this prospective clinical study (RPDP group: n = 12; edentulous group: n = 18). The prostheses were supported in strategically advantageous regions by placing implants with ball attachments and corresponding matrices in the existing dentures. The masticatory performance was evaluated with the Swallowing Threshold Test Index (STTI), the number of chewing strokes, and the time needed until swallowing at pre-treatment and 6 weeks after integration of ball attachments. Additionally, patients scored chewing satisfaction before and after implantation on a visual analogue scale. The STTI increased significantly (p ≤ 0.05) after implant therapy in the edentulous group but not in the RPDP group. Furthermore, the STTI was significantly higher (p ≤ 0.05) in the RPDP group than in the edentulous group at pre-treatment, however, not after therapy (P > 0.05). All patients were very satisfied after therapy concerning ability of speaking, chewing, and stability of their prosthesis. Patients of the edentulous group benefit more from strategically placed implants under the existing dentures than patients from the RPDP group. However, according to the subjective assessment, the chewing satisfaction generally increased for both groups after implant therapy. Patients with a strongly reduced dentition and edentulous patients benefit from strategically placed implants under the existing removable dentures.

  13. Alternating hemiplegia of childhood: early characteristics and evolution of a neurodevelopmental syndrome.

    Science.gov (United States)

    Sweney, Matthew T; Silver, Kenneth; Gerard-Blanluet, Marion; Pedespan, Jean-Michel; Renault, Francis; Arzimanoglou, Alexis; Schlesinger-Massart, Mylynda; Lewelt, Aga J; Reyna, Sandra P; Swoboda, Kathryn J

    2009-03-01

    Alternating hemiplegia of childhood is a predominantly sporadic neurodevelopmental syndrome of uncertain etiology. In more than 3 decades since its description, little progress has been made in understanding its etiology or in identifying effective treatments. In 1998, in collaboration with the Alternating Hemiplegia of Childhood Foundation, an international registry was established to help document clinical outcomes and promote research efforts. We present phenotypic data on 103 patients who met existing diagnostic criteria for alternating hemiplegia of childhood. Although some of these subjects may have been included in previously published reviews, our focus was directed toward the earliest manifestations of symptoms and evolution of features over time. Data sources included written questionnaires, face-to-face and telephone interviews, clinical examination, and medical charts. Characteristics of disease onset, medical comorbidities, episode triggers, diagnostic workup, and treatment are presented. Paroxysmal eye movements were the most frequent early symptom, manifesting in the first 3 months of life in 83% of patients. Hemiplegic episodes appeared by 6 months of age in 56% of infants. Background slowing shown by electroencephalography during typical paroxysmal events, including hemiplegic, tonic, or dystonic episodes was frequent (21 of 42 cases). Distinct convulsive episodes with altered consciousness believed to be epileptic in nature were reported in 41% of patients. Ataxia (96%) and cognitive impairment (100%) were frequent nonepisodic symptoms. Empiric pharmacologic treatment approaches offered little benefit in most subjects and resulted in adverse effects in 20% of patients. Prolonged episodes were completely or temporarily aborted during sleep in all subjects. This descriptive analysis of a large cohort of children indicates that paroxysmal ocular movements are an early, highly suggestive symptom, followed by paroxysmal episodes of focal dystonia or

  14. Differential susceptibility to the environment: an evolutionary--neurodevelopmental theory.

    Science.gov (United States)

    Ellis, Bruce J; Boyce, W Thomas; Belsky, Jay; Bakermans-Kranenburg, Marian J; van Ijzendoorn, Marinus H

    2011-02-01

    Two extant evolutionary models, biological sensitivity to context theory (BSCT) and differential susceptibility theory (DST), converge on the hypothesis that some individuals are more susceptible than others to both negative (risk-promoting) and positive (development-enhancing) environmental conditions. These models contrast with the currently dominant perspective on personal vulnerability and environmental risk: diathesis stress/dual risk. We review challenges to this perspective based on emerging theory and data from the evolutionary, developmental, and health sciences. These challenges signify the need for a paradigm shift in conceptualizing Person x Environment interactions in development. In this context we advance an evolutionary--neurodevelopmental theory, based on DST and BSCT, of the role of neurobiological susceptibility to the environment in regulating environmental effects on adaptation, development, and health. We then outline current thinking about neurogenomic and endophenotypic mechanisms that may underpin neurobiological susceptibility, summarize extant empirical research on differential susceptibility, and evaluate the evolutionary bases and implications of BSCT and DST. Finally, we discuss applied issues including methodological and statistical considerations in conducting differential susceptibility research; issues of ecological, cultural, and racial--ethnic variation in neurobiological susceptibility; and implications of differential susceptibility for designing social programs. We conclude that the differential susceptibility paradigm has far-reaching implications for understanding whether and how much child and adult development responds, for better and for worse, to the gamut of species-typical environmental conditions.

  15. Biodegradation of Volatile Organic Compounds and Their Effects on Biodegradability under Co-Existing Conditions

    Science.gov (United States)

    Yoshikawa, Miho; Zhang, Ming; Toyota, Koki

    2017-01-01

    Volatile organic compounds (VOCs) are major pollutants that are found in contaminated sites, particularly in developed countries such as Japan. Various microorganisms that degrade individual VOCs have been reported, and genomic information related to their phylogenetic classification and VOC-degrading enzymes is available. However, the biodegradation of multiple VOCs remains a challenging issue. Practical sites, such as chemical factories, research facilities, and illegal dumping sites, are often contaminated with multiple VOCs. In order to investigate the potential of biodegrading multiple VOCs, we initially reviewed the biodegradation of individual VOCs. VOCs include chlorinated ethenes (tetrachloroethene, trichloroethene, dichloroethene, and vinyl chloride), BTEX (benzene, toluene, ethylbenzene, and xylene), and chlorinated methanes (carbon tetrachloride, chloroform, and dichloromethane). We also summarized essential information on the biodegradation of each kind of VOC under aerobic and anaerobic conditions, together with the microorganisms that are involved in VOC-degrading pathways. Interactions among multiple VOCs were then discussed based on concrete examples. Under conditions in which multiple VOCs co-exist, the biodegradation of a VOC may be constrained, enhanced, and/or unaffected by other compounds. Co-metabolism may enhance the degradation of other VOCs. In contrast, constraints are imposed by the toxicity of co-existing VOCs and their by-products, catabolite repression, or competition between VOC-degrading enzymes. This review provides fundamental, but systematic information for designing strategies for the bioremediation of multiple VOCs, as well as information on the role of key microorganisms that degrade VOCs. PMID:28904262

  16. Alterations in the expression of a neurodevelopmental gene exert long-lasting effects on cognitive-emotional phenotypes and functional brain networks: translational evidence from the stress-resilient Ahi1 knockout mouse.

    Science.gov (United States)

    Lotan, A; Lifschytz, T; Mernick, B; Lory, O; Levi, E; Ben-Shimol, E; Goelman, G; Lerer, B

    2017-06-01

    Many psychiatric disorders are highly heritable and may represent the clinical outcome of early aberrations in the formation of neural networks. The placement of brain connectivity as an 'intermediate phenotype' renders it an attractive target for exploring its interaction with genomics and behavior. Given the complexity of genetic make up and phenotypic heterogeneity in humans, translational studies are indicated. Recently, we demonstrated that a mouse model with heterozygous knockout of the key neurodevelopmental gene Ahi1 displays a consistent stress-resilient phenotype. Extending these data, the current research describes our multi-faceted effort to link early variations in Ahi1 expression with long-term consequences for functional brain networks and cognitive-emotional phenotypes. By combining behavioral paradigms with graph-based analysis of whole-brain functional networks, and then cross-validating the data with robust neuroinformatic data sets, our research suggests that physiological variation in gene expression during neurodevelopment is eventually translated into a continuum of global network metrics that serve as intermediate phenotypes. Within this framework, we suggest that organization of functional brain networks may result, in part, from an adaptive trade-off between efficiency and resilience, ultimately culminating in a phenotypic diversity that encompasses dimensions such as emotional regulation and cognitive function.

  17. Increased nuchal translucency thickness and risk of neurodevelopmental disorders

    DEFF Research Database (Denmark)

    Hellmuth, S G; Pedersen, L H; Miltoft, C B

    2017-01-01

    OBJECTIVE: To investigate the association between fetal nuchal translucency (NT) thickness and neurodevelopmental disorders in euploid children. METHODS: This study included 222 505 euploid children who had undergone routine first-trimester screening during fetal life. Children were divided...... spectrum disorders (ASD), cerebral palsy, epilepsy and febrile seizures was obtained from national patient registries. RESULTS: There was no excess risk of neurodevelopmental disorders among euploid children with first-trimester NT 95(th) -99(th) percentile. For children with NT > 99(th) percentile...... in the risk of cerebral palsy (OR, 1.91 (95% CI, 0.61-5.95), 0.47%), epilepsy (OR, 1.51 (95% CI, 0.63-3.66), 0.78%) or febrile seizures (OR, 0.72 (95% CI, 0.44-1.16), 2.65%). CONCLUSIONS: In a large unselected cohort of euploid children, there was no increased risk of neurodevelopmental disorders among those...

  18. Effects of pyrene exposure and temperature on early development of two co-existing Arctic copepods

    DEFF Research Database (Denmark)

    Grenvald, Julie Cornelius; Nielsen, Torkel Gissel; Hjorth, Morten

    2013-01-01

    Oil exploration is expected to increase in the near future in Western Greenland. At present, effects of exposure to oil compounds on early life-stages of the ecologically important Calanus spp. are unknown. We investigated the effects of the oil compound pyrene, on egg hatching and naupliar devel...

  19. Does mutual compensation of the cognitive effects induced by pain and opioids exist?

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Malver, Lasse Paludan; Andresen, Trine

    2015-01-01

    RATIONALE: Studies have demonstrated that both pain and opioids have actions on the central nervous system that may interfere with cognitive function, but their effects have mainly been analysed separately and not as an integrated process. OBJECTIVE: The objective of this study is to test two...... hypotheses: (1) the analgesic effect of opioids improves cognitive function by decreasing pain, and (2) pain antagonizes cognitive effects of opioids. METHODS: Randomized, placebo-controlled, crossover study. Three experiments were conducted with 22 healthy males. Sustained attention, memory and motor....... CONCLUSION: Pain and remifentanil seemed to have additive deleterious cognitive effects. This study represents an initial step to enhance our basic understanding of some of the cognitive effects following a painful stimulus and an opioid infusion separately and combined in a sequence comparable to clinical...

  20. The challenge of the EMC effect: Existing data and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Malace, Simona P. [JLAB; Gaskell, David J. [JLAB; Higinbotham, Douglas W. [JLAB; Cloet, Ian C. [ANL

    2014-08-01

    Since the discovery that the ratio of inclusive charged lepton (per-nucleon) cross sections from a nucleus A to the deuteron is not unity - even in deep inelastic scattering kinematics - a great deal of experimental and theoretical effort has gone into understanding the phenomenon. The EMC effect, as it is now known, shows that even in the most extreme kinematic conditions the effects of the nucleon being bound in a nucleus can not be ignored. In this paper we collect the most precise data available for various nuclear to deuteron ratios, as well as provide a commentary on the current status of the theoretical understanding of this thirty year old effect.

  1. For new customers only : A study on the effect of acquisition campaigns on a service company's existing customers' CLV

    NARCIS (Netherlands)

    Lhoest-Snoeck, Sietske; van Nierop, Erjen; Verhoef, Pieter

    This study examines the effect of attractively priced acquisition campaigns on retention intention, and subsequently CLV, of existing customers. The main finding is that customers who are aware of the acquisition campaigns both have a significantly higher intention to stay and do actually stay

  2. Comparative toxicity of three differently shaped carbon nanomaterials on Daphnia magna: does a shape effect exist?

    Science.gov (United States)

    Bacchetta, Renato; Santo, Nadia; Valenti, Irene; Maggioni, Daniela; Longhi, Mariangela; Tremolada, Paolo

    2018-02-01

    The acute toxicity of three differently shaped carbon nanomaterials (CNMs) was studied on Daphnia magna, comparing the induced effects and looking for the toxic mechanisms. We used carbon nano-powder (CNP), with almost spherical primary particle morphology, multi-walled carbon nanotubes (CNTs), tubes of multi-graphitic sheets, and cubic-shaped carbon nanoparticles (CNCs), for which no ecotoxicological data are available so far. Daphnids were exposed to six suspensions (1, 2, 5, 10, 20 and 50 mg L -1 ) of each CNM, and then microscopically analyzed. Ultrastructural analyses evidenced cellular uptake of nanoparticle in CNP and CNT exposed groups, but not in samples exposed to CNCs. Despite this difference, very similar effects were observed in tissues exposed to the three used CNMs: empty spaces between cells, cell detachment from the basal lamina, many lamellar bodies and autophagy vacuoles. These pathological figures were qualitatively similar among the three groups, but they differed in frequency and severity. CNCs caused the most severe effects, such as partial or complete dissolution of the brush border and thinning of the digestive epithelium. Being the cubic shape not allowed to be internalized into cells, but more effective than others in determining physical damages, we can conclude that shape is an important factor for driving nanoparticle uptake by cells and for determining the acute toxicological endpoints. Shape also plays a key role in determining the kind and the severity of pathologies, which are linked to the physical interactions of CNMs with the exposed tissues.

  3. Effect of pre-existing baryon inhomogeneities on the dynamics of ...

    Indian Academy of Sciences (India)

    light elements, leading to an inhomogeneous nucleosynthesis scenario. Inhomogeneities generated during the quark–hadron (Q–H) transition may survive until nucleosynthesis, but those generated earlier (through baryogenesis mechanisms) are likely to be wiped out by the effects of neutrino inflation and baryon diffusion.

  4. Activity and concentration of polyphenolic antioxidants in apple juice 1 Effect of existing production methods

    NARCIS (Netherlands)

    Sluis, van der A.A.; Dekker, M.; Skrede, G.; Jongen, W.M.F.

    2002-01-01

    Apples are an important source of flavonoids in the human diet. The effect of processing apples into juice on polyphenolic antioxidant content and activity is described. Raw juice obtained from Jonagold apples by pulping and straight pressing or after pulp enzyming had an antioxidant activity that

  5. Does a Protestant work ethic exist? Evidence from the well-being effect of unemployment

    NARCIS (Netherlands)

    van Hoorn, Andre; Maseland, Robbert

    Evidence on Weber's original thesis on a Protestant work ethic is ambiguous and relies on questionable measures of work attitudes. We test the relation between Protestantism and work attitudes using a novel method,.operationalizing work ethic as the effect of unemployment on-individuals' subjective

  6. Management of Sleep Disorders in Children With Neurodevelopmental Disorders: A Review.

    Science.gov (United States)

    Blackmer, Allison Beck; Feinstein, James A

    2016-01-01

    Neurodevelopmental disorders (NDDs) are defined as a group of disorders caused by changes in early brain development, resulting in behavioral and cognitive alterations in sensory and motor systems, speech, and language. NDDs affect approximately 1-2% of the general population. Up to 80% of children with NDDs are reported to have disrupted sleep; subsequent deleterious effects on daytime behaviors, cognition, growth, and overall development of the child are commonly reported. Examples of NDDs discussed in this review include autism spectrum disorder, cerebral palsy, Rett syndrome, Angelman syndrome, Williams syndrome, and Smith-Magenis syndrome. The etiology of sleep disorders in children with NDDs is largely heterogeneous and disease specific. The diagnosis and management of sleep disorders in this population are complex, and little high-quality data exist to guide a consistent approach to therapy. Managing sleep disorders in children with NDDs is critical both for the child and for the family but is often frustrating due to the refractory nature of the problem. Sleep hygiene must be implemented as first-line therapy; if sleep hygiene alone fails, it should be combined with pharmacologic management. The available evidence for the use of common pharmacologic interventions, such as iron supplementation and melatonin, as well as less common interventions, such as melatonin receptor agonists, clonidine, gabapentin, hypnotics, trazodone, and atypical antipsychotics is reviewed. Further, parents and caregivers should be provided with appropriate education on the nature of the sleep disorders and the expectation for modest pharmacologic benefit, at best. Additional data from well-designed trials in children with NDDs are desperately needed to gain a better understanding of sleep pharmacotherapy including efficacy and safety implications. Until then, clinicians must rely on the limited available data, as well as clinical expertise, when managing sleep disorders in the

  7. A Comprehensive Review on the Effectiveness of Existing Noise Barriers commonly used in the Railway Industry

    Directory of Open Access Journals (Sweden)

    Shahidan Shahiron

    2017-01-01

    Full Text Available Nowadays, advanced development and sophisticated new technology have led to various types of environmental pollution such as water, air, land, thermal pollution and so on. Recently, however, noise pollution is becoming one of the major threats to the world especially in urban areas where it adversely affects the quality of life of the public. In Malaysia, the Department of Environment has identified that the average transportation noise levels in major cities in peninsular Malaysia are 71.6 dB (A and 70.4 dB (A during the day and night respectively. The noise is usually emitted by airplanes, trains, vehicles, motorcycles, trucks and etc. Even though rail transport requires less energy and emits less hazardous substances, it has contributed to noise pollution issues and several health hazards among urban inhabitants such as deafness, nervous breakdowns, mental disorder, heart troubles, high blood pressure, headaches, dizziness, inefficiency and insomnia. Therefore, many studies attempt to reduce noise pollution by applying noise barriers at noise polluted areas via various approaches. This paper aims to explore the effectiveness of noise barriers using noise absorption performance due to several factors such as type of absorbent materials, material thickness, density, porosity and design. This research has found that the thicker the specimen and the denser the absorbent material, the better the sound absorption performance. Besides that, barrier design also plays a major role in determining its effectiveness, where the effectiveness of noise barriers should be high and long enough to break the line-of-sight between the sound source and the receiver. There are several methods that can be used to measure the effectiveness of noise barriers such as the Adrienne Method (in-situ measurement method and impedance tube method (laboratory measurement method to measure the acoustic absorption. Nevertheless, the impedance tube measurement method provides

  8. Intellectual Profiles in the Autism Spectrum and Other Neurodevelopmental Disorders

    Science.gov (United States)

    Mouga, Susana; Café, Cátia; Almeida, Joana; Marques, Carla; Duque, Frederico; Oliveira, Guiomar

    2016-01-01

    The influence of specific autism spectrum disorder (ASD) deficits in Intelligence Quotients (IQ), Indexes and subtests from the Wechsler Intelligence Scale for Children-III was investigated in 445 school-aged children: ASD (N = 224) and other neurodevelopmental disorders (N = 221), matched by Full-Scale IQ and chronological age. ASD have lower…

  9. Long-term neurodevelopmental outcome after fetal arrhythmia

    NARCIS (Netherlands)

    Lopriore, Enrico; Aziz, Muhammed I.; Nagel, Helene T.; Blom, Nico A.; Rozendaal, Lieke; Kanhai, Humphrey H. H.; Vandenbussche, Frank P. H. A.

    2009-01-01

    OBJECTIVE: The purpose of this study was to determine the long-term neurodevelopmental outcome in fetuses with severe tachy- or bradyarrhythmia. STUDY DESIGN: This was a follow-up study to assess the neurologic, mental, and psychomotor development in cases with fetal cardiac arrhythmia. RESULTS: A

  10. Neurodevelopmental Problems in Maltreated Children Referred with Indiscriminate Friendliness

    Science.gov (United States)

    Kocovska, Eva; Puckering, Christine; Follan, Michael; Smillie, Maureen; Gorski, Charlotta; Barnes, James; Wilson, Philip; Young, David; Lidstone, Emma; Pritchett, Rachel; Hockaday, Harriet; Minnis, Helen

    2012-01-01

    We aimed to explore the extent of neurodevelopmental difficulties in severely maltreated adopted children. We recruited 34 adopted children, referred with symptoms of indiscriminate friendliness and a history of severe maltreatment in their early childhood and 32 typically developing comparison children without such a history, living in biological…

  11. Update on the Role of Environmental Toxins in Neurodevelopmental Disabilities

    Science.gov (United States)

    Kouris, Steven

    2007-01-01

    Toxic exposures during pregnancy and early childhood continue to play an important role as a preventable cause of neurodevelopmental disabilities in the U.S. and around the world. Identifying and eliminating these toxins should be a priority, but the task is made exceedingly difficult due to the severe limits of scientific knowledge in this area…

  12. Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

    Science.gov (United States)

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

    Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…

  13. Pharmacogenetics of the Neurodevelopmental Impact of Anticancer Chemotherapy

    Science.gov (United States)

    Robaey, Philippe; Krajinovic, Maja; Marcoux, Sophie; Moghrabi, Albert

    2008-01-01

    Pharmacogenetics holds the promise of minimizing adverse neurodevelopmental outcomes of cancer patients by identifying patients at risk, enabling the individualization of treatment and the planning of close follow-up and early remediation. This review focuses first on methotrexate, a drug often implicated in neurotoxicity, especially when used in…

  14. Food allergy and food-based therapies in neurodevelopmental disorders

    NARCIS (Netherlands)

    De Theije, Caroline G M; Bavelaar, Bas M.; Lopes da Silva, Sofia; Korte, Sijmen Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D.

    2014-01-01

    Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders which occur in childhood and may persist into adulthood. Although the etiology of these disorders is largely unknown, genetic and environmental factors are thought to play a role in

  15. Conceptualising compensation in neurodevelopmental disorders: Reflections from autism spectrum disorder.

    Science.gov (United States)

    Livingston, Lucy Anne; Happé, Francesca

    2017-06-19

    Within research into neurodevelopmental disorders, little is known about the mechanisms underpinning changes in symptom severity across development. When the behavioural presentation of a condition improves/symptoms lessen, this may be because core underlying atypicalities in cognition/neural function have ameliorated. An alternative possibility is 'compensation'; that the behavioural presentation appears improved, despite persisting deficits at cognitive and/or neurobiological levels. There is, however, currently no agreed technical definition of compensation or its behavioural, cognitive and neural characteristics. Furthermore, its workings in neurodevelopmental disorders have not been studied directly. Here, we review current evidence for compensation in neurodevelopmental disorders, using Autism Spectrum Disorder as an example, in order to move towards a better conceptualisation of the construct. We propose a transdiagnostic framework, where compensation represents the processes responsible for an observed mismatch between behaviour and underlying cognition in a neurodevelopmental disorder, at any point in development. Further, we explore potential cognitive and neural mechanisms driving compensation and discuss the broader relevance of the concept within research and clinical settings. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Adaptive Profiles in Autism and Other Neurodevelopmental Disorders

    Science.gov (United States)

    Mouga, Susana; Almeida, Joana; Café, Cátia; Duque, Frederico; Oliveira, Guiomar

    2015-01-01

    We investigated the influence of specific autism spectrum disorder (ASD) deficits in learning adaptive behaviour, besides intelligence quotient (IQ). Participated 217 school-aged: ASD (N = 115), and other neurodevelopmental disorders (OND) groups (N = 102) matched by Full-Scale IQ. We compared standard scores of Vineland Adaptive Behaviour Scale…

  17. Neurodevelopmental status of HIV-exposed but uninfected children ...

    African Journals Online (AJOL)

    Neurodevelopmental status of HIV-exposed but uninfected children: A pilot study. P Springer, B Laughton, M Tomlinson, J Harvey, M Esser. Abstract. Introduction. HIV affects children both directly and indirectly, with evidence of increased infectious mortality and morbidity in the HIV-exposed but uninfected (HEU) infant.

  18. Extreme hyperbilirubinaemia in Zimbabwean neonates: neurodevelopmental outcome at 4 months

    NARCIS (Netherlands)

    Wolf, M. J.; Beunen, G.; Casaer, P.; Wolf, B.

    1997-01-01

    As part of a prospective study of severely jaundiced Zimbabwean infants, the relationship between maximum total serum bilirubin (TSB) concentration in the neonatal period and neurodevelopmental outcome at the corrected age of 4 months was studied. Fifty infants with a TSB of > 400 micromol/l (23.4

  19. Piperazine side-effects in a patient with pre-existing renal insufficiency

    Directory of Open Access Journals (Sweden)

    Majid Malaki

    2014-01-01

    Full Text Available Piperazine as an antihelminth has many adverse effects, especially on patients with renal insufficiency. We report the use of piperazine in a girl with a moderately severe kidney disease due to Biedl Bardet syndrome. She developed coma and acute kidney injury due to acute interstitial nephritis (AIN, anemia and thrombocytopenia. The presence of fever, proteinuria, acidosis, anemia, sterile pyuria and non-oliguric renal failure strongly suggested AIN. Her problems abated mostly by discontinuing of piperazine and supportive therapy, except anemia and thrombocytopenia.

  20. The social contagion effect of suicidal behavior in adolescents: does it really exist?

    Science.gov (United States)

    Ali, Mir M; Dwyer, Debra S; Rizzo, John A

    2011-03-01

    Suicide is the third leading cause of death among adolescents and a non-trivial percentage of adolescents report knowing someone who has attempted suicide. In light of this, a growing body of literature has explored whether suicidal behavior in one person may be imitated by others in their social networks. We seek to determine the extent to which suicidal behavior in individuals is influenced by suicidal behaviors of their peer and family members. Using a nationally-representative sample of adolescents, we employ multivariate regression analysis with controls for known factors associated with suicidal behaviors to help isolate the effects of peer and family members on suicidal behaviors. Our methodology allows us to account for environmental confounders, simultaneity and to a limited extent, non-random peer selection. Our peer measures are drawn from the nomination of close friends by the individuals and suicidal behaviors among the peer group were constructed using the peers' own responses. We find that a 10% increase in suicide attempts by family members were associated with a 2.13% and 1.23% increase in adolescent suicidal ideation and attempts, respectively. Our results also show that a 10% increase in peer suicidal ideation and attempts lead to a 0.7% and 0.3% increase in such behavior by the individuals. However, these positive associations between peer and individual suicide behavior become smaller and insignificant after adjustments were made for environmental confounders and peer selection. Although we are able to establish the overall importance of environmental confounding factors, we are unable to identify the specific components or characteristics of the surroundings that can explain suicidality. The complex relationships between peer selection and suicidality also limit the determination of causality. An increase in suicidal behavior by family members is positively associated with suicidal behavior among adolescents and effective policies aimed at

  1. Postnatal Phencyclidine (PCP) as a Neurodevelopmental Animal Model of Schizophrenia Pathophysiology and Symptomatology: A Review.

    Science.gov (United States)

    Grayson, B; Barnes, S A; Markou, A; Piercy, C; Podda, G; Neill, J C

    Cognitive dysfunction and negative symptoms of schizophrenia remain an unmet clinical need. Therefore, it is essential that new treatments and approaches are developed to recover the cognitive and social impairments that are seen in patients with schizophrenia. These may only be discovered through the use of carefully validated, aetiologically relevant and translational animal models. With recent renewed interest in the neurodevelopmental hypothesis of schizophrenia, postnatal administration of N-methyl-D-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) has been proposed as a model that can mimic aspects of schizophrenia pathophysiology. The purpose of the current review is to examine the validity of this model and compare it with the adult subchronic PCP model. We review the ability of postnatal PCP administration to produce behaviours (specifically cognitive deficits) and neuropathology of relevance to schizophrenia and their subsequent reversal by pharmacological treatments. We review studies investigating effects of postnatal PCP on cognitive domains in schizophrenia in rats. Morris water maze and delayed spontaneous alternation tasks have been used for working memory, attentional set-shifting for executive function, social novelty discrimination for selective attention and prepulse inhibition of acoustic startle for sensorimotor gating. In addition, we review studies on locomotor activity and neuropathology. We also include two studies using dual hit models incorporating postnatal PCP and two studies on social behaviour deficits following postnatal PCP. Overall, the evidence we provide supports the use of postnatal PCP to model cognitive and neuropathological disturbances of relevance to schizophrenia. To date, there is a lack of evidence to support a significant advantage of postnatal PCP over the adult subchronic PCP model and full advantage has not been taken of its neurodevelopmental component. When thoroughly characterised, it is likely

  2. The effects of the overline running model of the high-speed trains on the existing lines

    Science.gov (United States)

    Qian, Yong-Sheng; Zeng, Jun-Wei; Zhang, Xiao-Long; Wang, Jia-Yuan; Lv, Ting-Ting

    2016-09-01

    This paper studies the effect on the existing railway which is made by the train with 216 km/h high-speed when running across over the existing railway. The influence on the railway carrying capacity which is made by the transportation organization mode of the existing railway is analyzed under different parking modes of high-speed trains as well. In order to further study the departure intervals of the train, the average speed and the delay of the train, an automata model under these four-aspects is established. The results of the research in this paper could serve as the theoretical references to the newly built high-speed railways.

  3. Effectiveness of an existing estuarine no-take fish sanctuary within the Kennedy Space Center, Florida

    Science.gov (United States)

    Johnson, D.R.; Funicelli, N.A.; Bohnsack, James A.

    1999-01-01

    Approximately 22% of the waters of the Merritt Island National Wildlife Refuge, which encompasses the Kennedy Space Center, Florida, have been closed to public access and fishing since 1962. These closed areas offer an opportunity to test the effectiveness of 'no-take' sanctuaries by analyzing two replicated estuarine areas. Areas open and closed to fishing were sampled from November 1986 to January 1990 with 653 random trammel-net sets, each enclosing 3,721 m2. Samples from no-fishing areas had significantly (P Centropomus undecimalis, and 2.6 times greater for striped mullet Mugil cephalus. Fishing had the primary effect on CPUE, independent of habitat and other environmental factors. Salinity and depth were important secondary factors affecting CPUE, followed by season or month, and temperature. The importance of specific factors varied with each species. Median and maximum size of red drum, spotted seatrout, black drum, and striped mullet were also significantly greater in the unfished areas. More and larger fish of spawning age were observed in the unfished areas for red drum, spotted seatrout, and black drum. Tagging studies documented export of important sport fish from protected areas to fished areas.

  4. Effectiveness of international environmental regimes: Existing knowledge, cutting-edge themes, and research strategies

    Science.gov (United States)

    Young, Oran R.

    2011-01-01

    International environmental regimes—especially those regimes articulated in multilateral environmental agreements—have been a subject of intense interest within the scientific community over the last three decades. However, there are substantial differences of opinion regarding the effectiveness of these governance systems or the degree to which they are successful in solving the problems leading to their creation. This article provides a critical review of the literature on this topic. It extracts and summarizes what is known about the effectiveness of environmental regimes in the form of a series of general and specific propositions. It identifies promising topics for consideration in the next phase of research in this field. Additionally, it comments on the research strategies available to pursue this line of analysis. The general conclusions are that international environmental regimes can and do make a difference, although often in conjunction with a number of other factors, and that a strategy of using a number of tools combined can help to improve understanding of the determinants of success. PMID:22143795

  5. Effectiveness of international environmental regimes: existing knowledge, cutting-edge themes, and research strategies.

    Science.gov (United States)

    Young, Oran R

    2011-12-13

    International environmental regimes--especially those regimes articulated in multilateral environmental agreements--have been a subject of intense interest within the scientific community over the last three decades. However, there are substantial differences of opinion regarding the effectiveness of these governance systems or the degree to which they are successful in solving the problems leading to their creation. This article provides a critical review of the literature on this topic. It extracts and summarizes what is known about the effectiveness of environmental regimes in the form of a series of general and specific propositions. It identifies promising topics for consideration in the next phase of research in this field. Additionally, it comments on the research strategies available to pursue this line of analysis. The general conclusions are that international environmental regimes can and do make a difference, although often in conjunction with a number of other factors, and that a strategy of using a number of tools combined can help to improve understanding of the determinants of success.

  6. Effect of Blast-Induced Vibration from New Railway Tunnel on Existing Adjacent Railway Tunnel in Xinjiang, China

    Science.gov (United States)

    Liang, Qingguo; Li, Jie; Li, Dewu; Ou, Erfeng

    2013-01-01

    The vibrations of existing service tunnels induced by blast-excavation of adjacent tunnels have attracted much attention from both academics and engineers during recent decades in China. The blasting vibration velocity (BVV) is the most widely used controlling index for in situ monitoring and safety assessment of existing lining structures. Although numerous in situ tests and simulations had been carried out to investigate blast-induced vibrations of existing tunnels due to excavation of new tunnels (mostly by bench excavation method), research on the overall dynamical response of existing service tunnels in terms of not only BVV but also stress/strain seemed limited for new tunnels excavated by the full-section blasting method. In this paper, the impacts of blast-induced vibrations from a new tunnel on an existing railway tunnel in Xinjiang, China were comprehensively investigated by using laboratory tests, in situ monitoring and numerical simulations. The measured data from laboratory tests and in situ monitoring were used to determine the parameters needed for numerical simulations, and were compared with the calculated results. Based on the results from in situ monitoring and numerical simulations, which were consistent with each other, the original blasting design and corresponding parameters were adjusted to reduce the maximum BVV, which proved to be effective and safe. The effect of both the static stress before blasting vibrations and the dynamic stress induced by blasting on the total stresses in the existing tunnel lining is also discussed. The methods and related results presented could be applied in projects with similar ground and distance between old and new tunnels if the new tunnel is to be excavated by the full-section blasting method.

  7. Neurodevelopmental outcome after cardiac surgery utilizing cardiopulmonary bypass in children

    Directory of Open Access Journals (Sweden)

    Aymen N Naguib

    2015-01-01

    Full Text Available Introduction: Modulating the stress response and perioperative factors can have a paramount impact on the neurodevelopmental outcome of infants who undergo cardiac surgery utilizing cardiopulmonary bypass. Materials and Methods: In this single center prospective follow-up study, we evaluated the impact of three different anesthetic techniques on the neurodevelopmental outcomes of 19 children who previously underwent congenital cardiac surgery within their 1 st year of life. Cases were done from May 2011 to December 2013. Children were assessed using the Stanford-Binet Intelligence Scales (5 th edition. Multiple regression analysis was used to test different parental and perioperative factors that could significantly predict the different neurodevelopmental outcomes in the entire cohort of patients. Results: When comparing the three groups regarding the major cognitive scores, a high-dose fentanyl (HDF patients scored significantly higher than the low-dose fentanyl (LDF + dexmedetomidine (DEX (LDF + DEX group in the quantitative reasoning scores (106 ± 22 vs. 82 ± 15 P = 0.046. The bispectral index (BIS value at the end of surgery for the -LDF group was significantly higher than that in LDF + DEX group (P = 0.011. For the entire cohort, a strong correlation was seen between the standard verbal intelligence quotient (IQ score and the baseline adrenocorticotropic hormone level, the interleukin-6 level at the end of surgery and the BIS value at the end of the procedure with an R 2 value of 0.67 and P < 0.04. There was an inverse correlation between the cardiac Intensive Care Unit length of stay and the full-scale IQ score (R = 0.4675 and P 0.027. Conclusions: Patients in the HDF group demonstrated overall higher neurodevelopmental scores, although it did not reach statistical significance except in fluid reasoning scores. Our results may point to a possible correlation between blunting the stress response and improvement of the neurodevelopmental

  8. Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives.

    Science.gov (United States)

    Ghibellini, Giulia; Brancati, Francesco; Castori, Marco

    2015-03-01

    In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research. © 2015 Wiley Periodicals, Inc.

  9. Effects of non-symbolic numerical information suggest the existence of magnitude-space synesthesia.

    Science.gov (United States)

    Gertner, Limor; Arend, Isabel; Henik, Avishai

    2012-08-01

    In number-space synesthesia, numbers are visualized in spatially defined arrays. In a recent study (Gertner et al. in Cortex, doi: 10.1016/j.cortex.2012.03.019 , 2012), we found that the size congruency effect (SiCE) for physical judgments (i.e., comparing numbers' physical sizes while ignoring their numerical values, for example, 8) was modulated by the spatial position of the presented numbers. Surprisingly, we found that the neutral condition, which is comprise solely of physical sizes (e.g., 3), was affected as well. This pattern gave rise to the idea that number-space synesthesia might entail not only discrete, ordered, meaningful symbols (i.e., Arabic numbers) but also continuous non-symbolic magnitudes (i.e., sizes, length, luminance, etc.). We tested this idea by assessing the performance of two number-space synesthetes and 12 matched controls in 3 comparative judgment tasks involving symbolic and non-symbolic stimuli: (1) Arabic numbers, (2) dot clusters, and (3) sizes of squares. The spatial position of the presented stimuli was manipulated to be compatible or incompatible with respect to the synesthetic number-space perceptions. Results revealed that for synesthetes, but not for controls, non-symbolic magnitudes (dot clusters) as well as symbolic magnitudes (i.e., Arabic numbers) interacted with space. Our study suggests that number-space synesthetes might have a general magnitude-space association that is not restricted to concrete symbolic stimuli. These findings support recent theories on the perception and evaluation of sizes in numerical cognition.

  10. Neurodevelopmental origins of lifespan changes in brain and cognition.

    Science.gov (United States)

    Walhovd, Kristine B; Krogsrud, Stine K; Amlien, Inge K; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J; Håberg, Asta K; Kremen, William S; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S; Rohani, Darius A; Skranes, Jon; Storsve, Andreas B; Sølsnes, Anne Elisabeth; Tamnes, Christian K; Thompson, Wesley K; Reuter, Chase; Dale, Anders M; Fjell, Anders M

    2016-08-16

    Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4-88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother-Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain-cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.

  11. Fighting corruption when existing corruption-control levels count: what do wealth-effects tell us in Africa?

    OpenAIRE

    Simplice A, Asongu

    2012-01-01

    Why are some nations more effective at battling corruption than others? Are there different determinants in the fight against corruption across developing nations? Do income-levels matter in the fight against corruption when existing corruption-control levels also matter? In other words, how does the wealth of nations matter in the fight against corruption when corruption is assessed throughout the conditional distribution of corruption-control from countries with low initial levels of corrup...

  12. Minor physical anomalies in schizophrenia and bipolar I disorder and the neurodevelopmental continuum of psychosis.

    Science.gov (United States)

    Akabaliev, Valentin Hristov; Sivkov, Stefan Todorov; Mantarkov, Mladen Yordanov

    2014-09-01

    Minor physical anomalies (MPAs) have been investigated by numerous studies in patients with schizophrenia in support of the neurodevelopmental hypothesis of the disorder, but have rarely been examined in patients with bipolar disorder or in direct comparisons between the two conditions. The main objective of the present study was to compare the prevalence of MPAs in psychiatrically healthy controls, patients with bipolar I disorder, and patients with schizophrenia. A slightly modified version of the Waldrop Physical Anomaly Scale was used to assess MPAs in psychiatrically healthy controls (n = 103), patients with bipolar I disorder (n = 61), and patients with schizophrenia (n = 128). In five out of six topographic regions (mouth, feet, head, eyes, and ears) there was a pattern of lowest regional MPA scores in controls, intermediate in bipolar I disorder, and highest in schizophrenia. The cephalofacial composite score and the total MPA score showed the same pattern, with all between-group differences being statistically significant. Seven individual MPAs in the discriminant analysis model contributed independently to the prediction of the triple-dependent status of 'psychiatrically healthy control, bipolar I disorder patient, schizophrenia patient': high/arched palate, fine electric hair, large gap between first and second toes, third toe ≥ second toe, epicanthus, malformed ears, and furrowed tongue. Our findings support the existence of a continuum of neurodevelopmental adversity within the clinical spectrum of psychosis, with bipolar I disorder occupying an intermediate position between psychiatric health and schizophrenia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Examining and comparing social perception abilities across childhood-onset neurodevelopmental disorders.

    Science.gov (United States)

    Baribeau, Danielle A; Doyle-Thomas, Krissy A R; Dupuis, Annie; Iaboni, Alana; Crosbie, Jennifer; McGinn, Holly; Arnold, Paul D; Brian, Jessica; Kushki, Azadeh; Nicolson, Rob; Schachar, Russell J; Soreni, Noam; Szatmari, Peter; Anagnostou, Evdokia

    2015-06-01

    Several neurodevelopmental disorders are associated with social processing deficits. The objective of this study was to compare patterns of social perception abilities across obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and control participants. A total of 265 children completed the Reading the Mind in the Eyes Test-Child Version (RMET). Parents or caregivers completed established trait/symptom scales. The predicted percentage of accuracy on the RMET was compared across disorders and by item difficulty and item valence (i.e., positive/negative/neutral mental states), then analyzed for associations with trait/symptom scores. The percentage of correct RMET scores varied significantly between diagnostic groups (p social communication impairment and hyperactivity/impulsivity, but not OCD traits/symptoms, were associated with lower scores on the RMET, irrespective of diagnosis. Social perception abilities in neurodevelopmental disorders exist along a continuum. Children with ASD have the greatest deficits, whereas children with OCD may be hypersensitive to social information. Social communication deficits and hyperactive/impulsive traits are associated with impaired social perception abilities; these findings highlight overlapping cognitive and behavioral manifestations across disorders. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Food allergy and food-based therapies in neurodevelopmental disorders.

    Science.gov (United States)

    de Theije, Caroline G M; Bavelaar, Bas M; Lopes da Silva, Sofia; Korte, Sijmen Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2014-05-01

    Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders which occur in childhood and may persist into adulthood. Although the etiology of these disorders is largely unknown, genetic and environmental factors are thought to play a role in the development of ASD and ADHD. Allergic immune reactions, in prenatal and postnatal phases, are examples of these environmental factors, and adverse reactions to foods are reported in these children. In this review, we address the clinical and preclinical findings of (food) allergy in ASD and ADHD and suggest possible underlying mechanisms. Furthermore, opportunities for nutritional interventions in neurodevelopmental disorders are provided. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Thyroid hormone for preventing of neurodevelopmental impairment in preterm infants.

    Science.gov (United States)

    Osborn, D A

    2000-01-01

    Observational studies have shown an association between transiently low thyroid hormone levels in preterm infants in the first weeks of life (transient hypothyroxemia) and an abnormal neurodevelopmental outcome. Thyroid hormone therapy might prevent this morbidity. To assess whether thyroid hormone therapy in preterm infants without congenital hypothyroidism results in clinically important changes in neonatal and long term outcomes in terms of both benefits and harms. The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching in the English language. All trials using random or quasi-random patient allocation, in which thyroid hormone therapy (either treatment or prophylaxis) was compared to a control in premature infants. Primary clinical outcomes included measures of neurodevelopmental outcome and mortality. Assessment of trial quality, data extraction and synthesis of data, using relative risk (RR) and weighted mean difference (WMD), were performed using standard methods of the Cochrane Collaboration and its Neonatal Review Group. Eight studies were identified that compared thyroid hormone treatment to control. Four randomized or quasi-randomized studies met inclusion criteria (Chowdhry 1984, Amato 1989, van Wassenaer 1997 and Vanhole 1997). All studies enrolled preterm infants thyroid hormones. Three studies used thyroxine, whereas Amato 1989 used triiodothyronine. Only two studies with neurodevelopmental follow-up were of good methodology (van Wassenaer 1997 and Vanhole 1997). All studies were of small size with the largest, van Wassenaer 1997, enrolling 200 infants. A lack of comparability of data (neurodevelopmental test or timing of follow-up) prevented meta-analytic pooling of the studies for

  16. Molecular Basis of Neurodegeneration and Neurodevelopmental Defects in Menkes Disease

    Science.gov (United States)

    Zlatic, Stephanie; Comstra, Heather Skye; Gokhale, Avanti; Petris, Michael J.; Faundez, Victor

    2015-01-01

    ATP7A mutations impair copper metabolism resulting in three distinct genetic disorders in humans. These diseases are characterized by neurological phenotypes ranging from intellectual disability to neurodegeneration. Severe ATP7A loss-of function alleles trigger Menkes disease, a copper deficiency condition where systemic and neurodegenerative phenotypes dominate clinical outcomes. The pathogenesis of these manifestations has been attributed to hypoactivity of a limited number of copper-dependent enzymes, a hypothesis that we refer as the oligoenzymatic pathogenic hypothesis. This hypothesis, which has dominated the field for 25 years, only explains some systemic Menkes phenotypes. However, we argue that this hypothesis does not fully account for the Menkes neurodegeneration or neurodevelopmental phenotypes. Here, we propose revisions of the oligoenzymatic hypothesis that could illuminate the pathogenesis of Menkes neurodegeneration and neurodevelopmental defects through unsuspected overlap with other neurological conditions including Parkinson’s, intellectual disability, and schizophrenia. PMID:25583185

  17. The Neurodevelopmental Impact of Neonatal Morphine Administration

    OpenAIRE

    Attarian, Stephanie; Tran, Lan Chi; Moore, Aimee; Stanton, George; Meyer, Eric; Moore, Robert P.

    2014-01-01

    Medical management of newborn infants often necessitates recurrent painful procedures, which may alter nociceptive pathways during a critical developmental period and adversely effect neuropsychological outcomes. To mitigate the effects of repeated painful stimuli, opioid administration for peri-procedural analgesia and ICU (intensive care unit) sedation is common in the NICU (neonatal intensive care unit). A growing body of basic and animal evidence suggests potential long-term harm associat...

  18. Neurodevelopmental problems in maltreated children referred with indiscriminate friendliness

    OpenAIRE

    Kocovska, E.; Puckering, C; Follan, M.; Smillie, M.; Gorski, C.; Lidstone, E; Pritchett, R.; Hockaday, H.; Minnis, H.

    2012-01-01

    We aimed to explore the extent of neurodevelopmental difficulties in severely maltreated adopted children. We recruited 34 adopted children, referred with symptoms of indiscriminate friendliness and a history of severe maltreatment in their early childhood and 32 typically developing comparison children without such a history, living in biological families. All 66 children, aged 5–12 years, underwent a detailed neuropsychiatric assessment. The overwhelming majority of the adopted/indiscrimina...

  19. Epigenetic Mechanisms and Therapeutic Perspectives for Neurodevelopmental Disorders

    OpenAIRE

    Kubota, Takeo; Takae, Hirasawa; Miyake, Kunio

    2012-01-01

    The number of children with mild neurodevelopmental disorders, such as autism, has been recently increasing in advanced countries. This increase is probably caused by environmental factors rather than genetic factors, because it is unlikely that genetic mutation rates suddenly increased within a short period. Epigenetics is a mechanism that regulates gene expression, depending not on the underlying DNA sequence but on the chemical modifications of DNA and histone proteins. Because mental stre...

  20. Subjective Experience of Episodic Memory and Metacognition: A Neurodevelopmental Approach

    Directory of Open Access Journals (Sweden)

    Celine eSouchay

    2013-12-01

    Full Text Available Episodic retrieval is characterized by the subjective experience of remembering. This experience enables the co-ordination of memory retrieval processes and can be acted on metacognitively. In successful retrieval, the feeling of remembering may be accompanied by recall of important contextual information. On the other hand, when people fail (or struggle to retrieve information, other feelings, thoughts and information may come to mind. In this review, we examine the subjective and metacognitive basis of episodic memory function from a neurodevelopmental perspective, looking at recollection paradigms (such as source memory, and the report of recollective experience and metacognitive paradigms such as the feeling of knowing. We start by considering healthy development, and provide a brief review of the development of episodic memory, with a particular focus on the ability of children to report first-person experiences of remembering. We then consider neurodevelopmental disorders such as amnesia acquired in infancy, autism, Williams syndrome, Down syndrome or 22q11.2 deletion syndrome. This review shows that different episodic processes develop at different rates, and that across a broad set of different neurodevelopmental disorders there are various types of episodic memory impairment, each with possibly a different character. This literature is in agreement with the idea that episodic memory is a multifaceted process.

  1. Effects of pre-existing discontinuities on the residual strength of rock mass - Insight from a discrete element method simulation

    Science.gov (United States)

    Gao, F. Q.; Kang, H. P.

    2016-04-01

    When rock failure is unavoidable, the designer of engineering structures must know and account for the residual strength of the rock mass. This is particularly relevant in underground coal mine openings. Pre-existing discontinuities play an important role in the mechanical behavior of rock masses and thus it is important to understand the effects of such pre-existing discontinuities on the residual strength. For this purpose, the present study demonstrates a numerical analysis using a discrete element method simulation. The numerical results indicate that fracture intensity has no significant influence on the residual strength of jointed rock masses, independent of confining conditions. As confining pressures increase, both peak and residual strengths increase, with residual strength increasing at a faster rate. The finding was further demonstrated by analyzing documented laboratory compressive test data from a variety of rocks along with field data from coal pillars. A comprehensive interpretation of the finding was conducted using a cohesion-weakening-friction-strengthening (CWFS) model. The effect of rock bolts on rock mass strength was also evaluated by using a discrete element method model which suggested that rock bolts can significantly increases residual strength but have limited effect on increasing the peak strength of rock masses.

  2. The role of pre-existing disturbances in the effect of marine reserves on coastal ecosystems: a modelling approach.

    Directory of Open Access Journals (Sweden)

    Marie Savina

    Full Text Available We have used an end-to-end ecosystem model to explore responses over 30 years to coastal no-take reserves covering up to 6% of the fifty thousand square kilometres of continental shelf and slope off the coast of New South Wales (Australia. The model is based on the Atlantis framework, which includes a deterministic, spatially resolved three-dimensional biophysical model that tracks nutrient flows through key biological groups, as well as extraction by a range of fisheries. The model results support previous empirical studies in finding clear benefits of reserves to top predators such as sharks and rays throughout the region, while also showing how many of their major prey groups (including commercial species experienced significant declines. It was found that the net impact of marine reserves was dependent on the pre-existing levels of disturbance (i.e. fishing pressure, and to a lesser extent on the size of the marine reserves. The high fishing scenario resulted in a strongly perturbed system, where the introduction of marine reserves had clear and mostly direct effects on biomass and functional biodiversity. However, under the lower fishing pressure scenario, the introduction of marine reserves caused both direct positive effects, mainly on shark groups, and indirect negative effects through trophic cascades. Our study illustrates the need to carefully align the design and implementation of marine reserves with policy and management objectives. Trade-offs may exist not only between fisheries and conservation objectives, but also among conservation objectives.

  3. Preterm birth–associated neurodevelopmental impairment estimates at regional and global levels for 2010

    Science.gov (United States)

    Blencowe, Hannah; Lee, Anne CC; Cousens, Simon; Bahalim, Adil; Narwal, Rajesh; Zhong, Nanbert; Chou, Doris; Say, Lale; Modi, Neena; Katz, Joanne; Vos, Theo; Marlow, Neil; Lawn, Joy E.

    2013-01-01

    Background: In 2010, there were an estimated 15 million preterm births worldwide (preterm babies according to the level of care. A compartmental model was used to estimate the number of impaired postneonatal survivors following preterm birth in 2010. A separate model (DisMod-MR) was used to estimate years lived with disability (YLDs) for the global burden of disease 2010 study. Disability adjusted life years (DALYs) were calculated as the sum of YLDs and years of life lost (YLLs). Results: In 2010, there were an estimated 13 million preterm births who survived beyond the first month. Of these, 345,000 (2.7%, uncertainty range: 269,000–420,000) were estimated to have moderate or severe neurodevelopmental impairment, and a further 567,000 (4.4%, (445,000–732,000)) were estimated to have mild neurodevelopmental impairment. Many more have specific learning or behavioral impairments or reduced physical or mental health. Fewest data are available where the burden is heaviest. Preterm birth was responsible for 77 million DALYs, 3.1% of the global total, of which only 3 million were YLDs. Conclusion: Most preterm births (>90%) survive without neurodevelopmental impairment. Developing effective means of prevention of preterm birth should be a longer term priority, but major burden reduction could be made immediately with improved coverage and quality of care. Improved newborn care would reduce mortality, especially in low-income countries and is likely to reduce impairment in survivors, particularly in middle-income settings. PMID:24366461

  4. Biological mechanisms associated with increased perseveration and hyperactivity in a genetic mouse model of neurodevelopmental disorder.

    Science.gov (United States)

    Trent, Simon; Dean, Rachel; Veit, Bonnie; Cassano, Tommaso; Bedse, Gaurav; Ojarikre, Obah A; Humby, Trevor; Davies, William

    2013-08-01

    Chromosomal deletions at Xp22.3 appear to influence vulnerability to the neurodevelopmental disorders attention deficit hyperactivity disorder (ADHD) and autism. 39,X(Y*)O mice, which lack the murine orthologue of the Xp22.3 ADHD candidate gene STS (encoding steroid sulfatase), exhibit behavioural phenotypes relevant to such disorders (e.g. hyperactivity), elevated hippocampal serotonin (5-HT) levels, and reduced serum levels of dehydroepiandrosterone (DHEA). Here we initially show that 39,X(Y*)O mice are also deficient for the recently-characterised murine orthologue of the Xp22.3 autism candidate gene ASMT (encoding acetylserotonin-O-methyltransferase). Subsequently, to specify potential behavioural correlates of elevated hippocampal 5-HT arising due to the genetic lesion, we compared 39,X(Y*)O MF1 mice to 40,XY MF1 mice on behavioural tasks taxing hippocampal and/or 5-HT function (a 'foraging' task, an object-location task, and the 1-choice serial reaction time task of impulsivity). Although Sts/Asmt deficiency did not influence foraging behaviour, reactivity to familiar objects in novel locations, or 'ability to wait', it did result in markedly increased response rates; these rates correlated with hippocampal 5-HT levels and are likely to index behavioural perseveration, a frequent feature of neurodevelopmental disorders. Additionally, we show that whilst there was no systematic relationship between serum DHEA levels and hippocampal 5-HT levels across 39,X(Y*)O and 40,XY mice, there was a significant inverse linear correlation between serum DHEA levels and activity. Our data suggest that deficiency for genes within Xp22.3 could influence core behavioural features of neurodevelopmental disorders via dissociable effects on hippocampal neurochemistry and steroid hormone levels, and that the mediating neurobiological mechanisms may be investigated in the 39,X(Y*)O model. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Flood protection effect of the existing and projected reservoirs in the Amur River basin: evaluation by the hydrological modeling system

    Directory of Open Access Journals (Sweden)

    Y. Motovilov

    2015-06-01

    Full Text Available Hydrological modeling system was developed as a tool addressed supporting flood risk management by the existing and projected reservoirs in the Amur River basin. The system includes the physically-based semi-distributed model of runoff generation ECOMAG coupled with a hydrodynamic MIKE-11 model to simulate channel flow in the main river. The case study was carried out for the middle part of the Amur River where large reservoirs are located on the Zeya and Bureya Rivers. The models were calibrated and validated using streamflow measuruments at the different gauges of the main river and its tributaries. Numerical experiments were carried out to assess the effect of the existing Zeya and Bureya reservoirs regulation on 850 km stretch of the middle Amur River stage. It was shown that in the absence of the reservoirs, the water levels downstream of the Zeya and Bureya Rivers would be 0.5–1.5 m higher than the levels measured during the disastrous flood of 2013. Similar experiments were carried out to assess possible flood protection effect of new projected reservoirs on the Zeya and Bureya Rivers.

  6. Flood protection effect of the existing and projected reservoirs in the Amur River basin: evaluation by the hydrological modeling system

    Science.gov (United States)

    Motovilov, Y.; Danilov-Danilyan, V.; Dod, E.; Kalugin, A.

    2015-06-01

    Hydrological modeling system was developed as a tool addressed supporting flood risk management by the existing and projected reservoirs in the Amur River basin. The system includes the physically-based semi-distributed model of runoff generation ECOMAG coupled with a hydrodynamic MIKE-11 model to simulate channel flow in the main river. The case study was carried out for the middle part of the Amur River where large reservoirs are located on the Zeya and Bureya Rivers. The models were calibrated and validated using streamflow measuruments at the different gauges of the main river and its tributaries. Numerical experiments were carried out to assess the effect of the existing Zeya and Bureya reservoirs regulation on 850 km stretch of the middle Amur River stage. It was shown that in the absence of the reservoirs, the water levels downstream of the Zeya and Bureya Rivers would be 0.5-1.5 m higher than the levels measured during the disastrous flood of 2013. Similar experiments were carried out to assess possible flood protection effect of new projected reservoirs on the Zeya and Bureya Rivers.

  7. Does the Kuleshov Effect Really Exist? Revisiting a Classic Film Experiment on Facial Expressions and Emotional Contexts.

    Science.gov (United States)

    Barratt, Daniel; Rédei, Anna Cabak; Innes-Ker, Åse; van de Weijer, Joost

    2016-08-01

    According to film mythology, the Soviet filmmaker Lev Kuleshov conducted an experiment in which he combined a close-up of an actor's neutral face with three different emotional contexts: happiness, sadness, and hunger. The viewers of the three film sequences reportedly perceived the actor's face as expressing an emotion congruent with the given context. It is not clear, however, whether or not the so-called "Kuleshov effect" really exists. The original film footage is lost and recent attempts at replication have produced either conflicting or unreliable results. The current paper describes an attempt to replicate Kuleshov's original experiment using an improved experimental design. In a behavioral and eye tracking study, 36 participants were each presented with 24 film sequences of neutral faces across six emotional conditions. For each film sequence, the participants were asked to evaluate the emotion of the target person in terms of valence, arousal, and category. The participants' eye movements were recorded throughout. The results suggest that some sort of Kuleshov effect does in fact exist. For each emotional condition, the participants tended to choose the appropriate category more frequently than the alternative options, while the answers to the valence and arousal questions also went in the expected directions. The eye tracking data showed how the participants attended to different regions of the target person's face (in light of the intermediate context), but did not reveal the expected differences between the emotional conditions.

  8. Comparison and Extension of Existing 3D Propagation Models with Real-World Effects Based on Ray-tracing

    DEFF Research Database (Denmark)

    Kifle, Dereje W.; Gimenez, Lucas Chavarria; Wegmann, Bernhard

    2014-01-01

    , such kind of automated and flexible network operation require a Self Organizing Network algorithm based on network performance parameters being partly derived from the radio measurements. Appropriate radio propagation models are not only needed for network planning tools but also for simulative lab tests...... of the developed Self Organizing Network algorithm controlling the flexible deployment changes enabled by Active Antenna Systems. In this paper, an extension of the existing 3D propagation model is proposed in order to incorporate the the propagation condition variation effects, not considered so far, by changing...... antenna beam orientation like antenna tilting or when users are distributed in the third dimension (height) in multi-floor scenarios. Ray tracing based generated propagation maps that show the realistic propagation effect are used as 3D real world reference for investigation and model approval....

  9. Central tetrahydrobiopterin concentration in neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Richard E Frye

    2010-07-01

    Full Text Available Tetrahydrobiopterin (BH4 is a naturally occurring cofactor essential for critical metabolic pathways. Studies suggest that BH4 supplementation may ameliorate autism symptoms; the biological mechanism for such an effect is unknown. To help understand the relation between central BH4 concentration and systemic metabolism and to develop a biomarker of central BH4 concentration, the relationship between cerebrospinal fluid BH4 concentration and serum amino acids was studied. BH4 concentration was found to be distributed in two groups, a lower and higher BH4 concentration group. Two serum amino acids, citrulline and methionine, differentiated these groups, and the ratio of serum citrulline-to-methionine was found to correlate with the cerebrospinal fluid BH4 concentration (r = -0.67, p < 0.05. Both citrulline and methionine are substrates in inflammation and oxidative stress pathways - two pathways that utilize BH4 and are abnormally activated in autism. These data suggests that central BH4 concentration may be related to systemic inflammation and oxidative stress pathways.

  10. Family adjustment and interventions in neurodevelopmental disorders.

    Science.gov (United States)

    Dykens, Elisabeth M

    2015-03-01

    Developmental disabilities are increasingly recognized, and remarkable progress is being made on the genetic and neurobiological underpinnings of many disorders. Yet, only a tiny percentage of the disability literature addresses families of children with disabilities. A review of recently published family studies reveals salient trends and gaps. Consistent with previous work, high levels of parent stress, illness, anxiety, and depression are apparent. Studies in the USA focused on parents of children with autism; in contrast, studies on parents of children with intellectual disabilities were almost always conduced abroad. Compared to other disabilities, families of children with psychiatric disorders and genetic syndromes are understudied. The majority of family studies are descriptive, with very few trials or interventions aimed at reducing parental stress. Of these, mindfulness practices and a peer-mentor model of treatment delivery hold much promise for effective stress reduction. Psychoeducational programs and respite care are differentially beneficial. A new era of family intervention research is in order. This work can take advantage of many advances in telemedicine, peer-mentor models, smart technology, and biomarkers as indices of change. Benefit could also stem from group interventions with parents who share similar concerns, regardless of their child's diagnostic label.

  11. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

    Directory of Open Access Journals (Sweden)

    Dichter Gabriel S

    2012-07-01

    Full Text Available Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders, neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder, and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome. We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

  12. Chronic vortioxetine treatment in rodents modulates gene expression of neurodevelopmental and plasticity markers.

    Science.gov (United States)

    Waller, Jessica A; Tamm, Joseph A; Abdourahman, Aicha; Pehrson, Alan L; Li, Yan; Cajina, Manuel; Sánchez, Connie

    2017-02-01

    The multimodal antidepressant vortioxetine displays an antidepressant profile distinct from those of conventional selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and possesses cognitive-enhancing properties in preclinical and clinical studies. Recent studies have begun to investigate molecular mechanisms that may differentiate vortioxetine from other antidepressants. Acute studies in adult rats and chronic studies in a middle-aged mouse model reveal upregulation of several markers that play a central role in synaptic plasticity. However, the effect of chronic vortioxetine treatment on expression of neuroplasticity and neurodevelopmental biomarkers in naïve rats has not been evaluated. In the present study, we demonstrate that vortioxetine at a range of doses regulates expression of genes associated with plasticity in the frontal cortex, hippocampus, region encompassing the amygdala, as well as in blood, and displays similar effects relative to the SSRI fluoxetine in adult naïve rats. These genes encode immediate early genes (IEGs), translational regulators, and the neurodevelopmental marker Sema4g. Similar findings detected in brain regions and in blood provide a potential translational impact, and vortioxetine appears to consistently regulate signaling in these networks of neuroplasticity and developmental markers. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  13. Etiological Subgroups of Small-for-Gestational-Age: Differential Neurodevelopmental Outcomes.

    Directory of Open Access Journals (Sweden)

    Xiuhong Li

    Full Text Available It remains unclear why substantial variations in neurodevelopmental outcomes exist within small-for-gestational-age (SGA children. We prospectively compared 5-y neurodevelopmental outcomes across SGA etiological subgroups.Children born SGA (N = 1050 from U.S. Early Childhood Longitudinal Study-Birth Cohort (2001-2007 was divided into etiological subgroups by each of 7 well-established prenatal risk factors. We fit linear regression models to compare 5-y reading, math, gross motor and fine motor scores across SGA subgroups, adjusting for socio-demographic confounders.Compared to singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading (adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06] and math (-2.22 [-3.61, -0.84] scores. These disadvantages in reading and math existed only among multiple-birth SGA subgroup without ovulation stimulation (reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44], but not among those with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86, 3.12]. Compared to singleton SGA subgroup without maternal smoking and inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of maternal smoking and inadequate gestational weight gain (GWG had lower mean reading (-4.81 [-8.50, -1.12] and math (-2.95 [-5.51, -0.38] scores. These differences were not mediated by Apgar score.Multiple-birth SGA subgroups (vs. singleton SGA or singleton SGA subgroup with co-occurrence of smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking and inadequate gestational weight gain have poorer cognitive development up to 5 y.

  14. The effect of cupping therapy for low back pain: A meta-analysis based on existing randomized controlled trials.

    Science.gov (United States)

    Wang, Yun-Ting; Qi, Yong; Tang, Fu-Yong; Li, Fei-Meng; Li, Qi-Huo; Xu, Chang-Peng; Xie, Guo-Ping; Sun, Hong-Tao

    2017-11-06

    LBP is one of the most common symptoms with high prevalence throughout the world. Conflicting conclusions exist in RCTs on cupping for LBP. To assess the effects and safety of cupping for the patients with LBP. Pubmed, Cochrane Library databases, and Embase database were electronically researched. RCTs reporting the cupping for the patients with LBP were included. The meta-analysis was conducted using Review Manager software (version 5.3, Nordic Cochrane Centre). The primary outcome was VAS scores. The secondary outcomes included ODI scores, MPPI scores and complications. Six RCTs were included in this synthesized analysis. The results showed that cupping therapy was superior to the control management with respect to VAS scores (SMD: -0.73, [95% CI: -1.42 to -0.04]; P= 0.04), and ODI scores (SMD: -3.64, [95% CI: -5.85 to -1.42]; P= 0.001). There was no statistical significant difference as regard to MPPI scores. No serious adverse event was reported in the included studies. Cupping therapy can significantly decrease the VAS scores and ODI scores for patients with LBP compared to the control management. High heterogeneity and risk of bias existing in studies limit the authenticity of the findings.

  15. Implant placement under existing removable dental prostheses and its effect on oral health-related quality of life.

    Science.gov (United States)

    Wolfart, Stefan; Moll, Daniel; Hilgers, Ralf-Dieter; Wolfart, Mona; Kern, Matthias

    2013-12-01

    One aim of this prospective clinical study was to measure the effects of strategicimplant placement under removable partial dental prostheses (RPDPs) and among removable complete dental prostheses (RCDPs) on oral health-related quality of life (OHRQoL). Twenty-three patients participated in this study restored with RCDPs (n = 12) or RPDPs retained by telescopic crowns with 1-2 abutment teeth (n = 11). The total number of abutments was increased to 5-6 (maxilla) or to 4 (mandible) by placing implants in strategically advantageous regions. Ball attachments were attached to the implants and integrated in the existing denture. The Oral Health Impact Profile (49 questions) was completed by patients before implant placement, at baseline (integration of ball attachments), and during 12- and 24-month follow-up visits. There were marked reductions of impacts in both groups when comparing pre-treatment scores and scores at baseline (P 0.05). It can be concluded that a strategic placement of implants under the existing dental prostheses improves OHRQoL in both treatment groups. © 2012 John Wiley & Sons A/S.

  16. Microglial Intracellular Ca2+ Signaling in Synaptic Development and its Alterations in Neurodevelopmental Disorders.

    Science.gov (United States)

    Mizoguchi, Yoshito; Monji, Akira

    2017-01-01

    Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by deficits in social interaction, difficulties with language and repetitive/restricted behaviors. Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) when they are activated in response to immunological stimuli. Recent in vivo imaging has shown that microglia sculpt and refine the synaptic circuitry by removing excess and unwanted synapses and be involved in the development of neural circuits or synaptic plasticity thereby maintaining the brain homeostasis. BDNF, one of the neurotrophins, has various important roles in cell survival, neurite outgrowth, neuronal differentiation, synaptic plasticity and the maintenance of neural circuits in the CNS. Intracellular Ca2+ signaling is important for microglial functions including ramification, de-ramification, migration, phagocytosis and release of cytokines, NO and BDNF. BDNF induces a sustained intracellular Ca2+ elevation through the upregulation of the surface expression of canonical transient receptor potential 3 (TRPC3) channels in rodent microglia. BDNF might have an anti-inflammatory effect through the inhibition of microglial activation and TRPC3 could play important roles in not only inflammatory processes but also formation of synapse through the modulation of microglial phagocytic activity in the brain. This review article summarizes recent findings on emerging dual, inflammatory and non-inflammatory, roles of microglia in the brain and reinforces the importance of intracellular Ca2+ signaling for microglial functions in both normal neurodevelopment and their potential contributing to neurodevelopmental disorders such as ASDs.

  17. Novel roles for immune molecules in neural development: Implications for neurodevelopmental disoders

    Directory of Open Access Journals (Sweden)

    Paula A Garay

    2010-09-01

    Full Text Available Although the brain has classically been considered "immune-privileged," current research suggests extensive communication between the nervous and the immune systems in both health and disease. Recent studies demonstrate that immune molecules are present at the right place and time to modulate the development and function of the healthy and diseased CNS. Indeed, immune molecules play integral roles in the CNS throughout neural development, including affecting neurogenesis, neuronal migration, axon guidance, synapse formation, activity-dependent refinement of circuits, and synaptic plasticity. Moreover, the roles of individual immune molecules in the nervous system may change over development. This review focuses on the effects of immune molecules on neuronal connections in the mammalian central nervous system—specifically the roles for MHCI and its receptors, complement, and cytokines on the function, refinement, and plasticity of cortical and hippocampal synapses and their relationship to neurodevelopmental disorders. These functions for immune molecules during neural development suggest that they could also mediate pathological responses to chronic elevations of cytokines in neurodevelopmental disorders, including autism spectrum disorders (ASD and schizophrenia.

  18. The Groningen LCPUFA study : no effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years

    NARCIS (Netherlands)

    de Jong, Corina; Kikkert, Hedwig K.; Fidler, Vaclav; Hadders-Algra, Mijna

    Long-chain PUFA (LCPUFA) supplementation of formula can have beneficial effects on neurodevelopmental outcome in early infancy, but uncertainty exists regarding effects after 6 months. The present study is the first to investigate whether consumption by term infants of formula containing LCPUFA for

  19. Translational animal models of autism and neurodevelopmental disorders.

    Science.gov (United States)

    Crawley, Jacqueline N

    2012-09-01

    Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics.

  20. Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    E. Rossignol

    2011-01-01

    Full Text Available A dysfunction of cortical and limbic GABAergic circuits has been postulated to contribute to multiple neurodevelopmental disorders in humans, including schizophrenia, autism, and epilepsy. In the current paper, I summarize the characteristics that underlie the great diversity of cortical GABAergic interneurons and explore how the multiple roles of these cells in developing and mature circuits might contribute to the aforementioned disorders. Furthermore, I review the tightly controlled genetic cascades that determine the fate of cortical interneurons and summarize how the dysfunction of genes important for the generation, specification, maturation, and function of cortical interneurons might contribute to these disorders.

  1. Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement

    National Research Council Canada - National Science Library

    Ikumi Hori; Takanobu Otomo; Mitsuko Nakashima; Fuyuki Miya; Yutaka Negishi; Hideaki Shiraishi; Yutaka Nonoda; Shinichi Magara; Jun Tohyama; Nobuhiko Okamoto; Takeshi Kumagai; Konomi Shimoda; Yoshiya Yukitake; Daigo Kajikawa; Tomohiro Morio; Ayako Hattori; Motoo Nakagawa; Naoki Ando; Ichizo Nishino; Mitsuhiro Kato; Tatsuhiko Tsunoda; Hirotomo Saitsu; Yonehiro Kanemura; Mami Yamasaki; Kenjiro Kosaki; Naomichi Matsumoto; Tamotsu Yoshimori; Shinji Saitoh

    2017-01-01

    Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency...

  2. Neuro-developmental outcome at 18 months in premature infants with diffuse excessive high signal intensity on MR imaging of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Hart, Anthony [Sheffield Teaching Hospitals NHS Foundation Trust, Department of Neonatology, Sheffield (United Kingdom); University of Sheffield, Department of Academic Radiology, Sheffield, South Yorkshire (United Kingdom); Whitby, Elspeth; Paley, Martyn [University of Sheffield, Department of Academic Radiology, Sheffield, South Yorkshire (United Kingdom); Wilkinson, Stuart; Smith, Michael [Sheffield Teaching Hospitals NHS Foundation Trust, Department of Neonatology, Sheffield (United Kingdom); Alladi, Sathya [Sheffield Teaching Hospitals NHS Foundation Trust, Department of Child Development, Sheffield (United Kingdom)

    2011-10-15

    Diffuse excessive high signal intensity (DEHSI) may represent damage to the white matter in preterm infants, but may be best studied alongside quantitative markers. Limited published data exists on its neuro-developmental implications. The purpose of this study was to assess whether preterm children with DEHSI at term-corrected age have abnormal neuro-developmental outcome. This was a prospective observational study of 67 preterm infants with MRI of the brain around term-equivalent age, including diffusion-weighted imaging (DWI). Images were reported as being normal, overtly abnormal or to show DEHSI. A single observer placed six regions of interest in the periventricular white matter and calculated the apparent diffusion coefficients (ADC). DEHSI was defined as (1) high signal on T2-weighted images alone, (2) high signal with raised ADC values or (3) raised ADC values independent of visual appearances. The neuro-development was assessed around 18 months' corrected age using the Bayley Scales of Infant and Toddler Development (3rd Edition). Standard t tests compared outcome scores between imaging groups. No statistically significant difference in neuro-developmental outcome scores was seen between participants with normal MRI and DEHSI, regardless of which definition was used. Preterm children with DEHSI have similar neuro-developmental outcome to those with normal brain MRI, even if the definition includes objective markers alongside visual appearances. (orig.)

  3. A prospective clinical study to evaluate the effect of manual and power toothbrushes on pre-existing gingival recessions.

    Science.gov (United States)

    Dorfer, Christof E; Joerss, Daniela; Wolff, Diana

    2009-07-01

    To evaluate gingival recession changes after six months of brushing with an oscillating-rotating power toothbrush (PT) or an ADA reference manual toothbrush (MT). Healthy subjects with pre-existing recession were assigned to brush with either a PT (n=55) or an ADA reference MT (n=54) according to a prospective randomized, controlled, single-blind, parallel group design. Participants were asked to brush their teeth twice daily for two minutes each with the same fluoride toothpaste. Clinical attachment loss and probing pocket depths (PPDs) were measured at six sites per tooth to the nearest mm by one calibrated examiner at baseline and after six months. Gingival recession was calculated as the differences between clinical attachment loss and PPDs overall and separately at individual sites. As compared with baseline, overall recession at six months was reduced from 2.35 +/- 0.35 mm to 1.98 +/- 0.55 mm (p<0.001) in the PT group and from 2.26 +/- 0.31 mm to 1.90 +/- 0.45 mm (p<0.001) in the MT group. The data showed 40% (power) and 38% (manual) of all recession sites improved by at least 0.5 mm while 51% and 54% remained unchanged. Eight percent and 7% recessions increased over time. Differences between groups were not statistically significant at either timepoint. Both the PT and the MT significantly reduced pre-existing gingival recession after six months of brushing. This may have been due to improved brushing technique (i.e., Hawthorne effect). Based on these six-month data, concern that power tooth brushing results in a higher risk for gingival recession is not warranted.

  4. [Effect of pre-existing hypertension on the prevalence and incidence of microalbuminuria in non insulin-dependent diabetic patients].

    Science.gov (United States)

    Suraniti, S; Daligaud, L; Chameau, A M; Marre, M; Fressinaud, P

    1991-08-01

    Microalbuminuria predicts increased rate of hypertension and mortality in insulino-dependent diabetics. In non insulin-dependent diabetes, hypertension often exists before onset of diabetes. To study effects of preexisting hypertension on prevalence and occurrence of elevated urinary albumin excretion (UAE), we collected datas from 614 non insulin-dependent diabetics, in a cross sectional survey: age was 60 +/- 10.4 years, (range 40-75 years), body mass index (BMI) 29 +/- 5.8 kg/m2, hemoglobin A1C 8 +/- 1.9%, systolic blood pressure (SBP) 134 +/- 18 mmHg, diastolic blood pressure (DBP) 76 +/- 10 mmHg, and serum creatinine 91 +/- 44 mumol/l. In the whole group, prevalence of hypertension was 59%. Microalbuminuria (EUA 20-200 mg/l) was present in 25.9% of the cases, microalbuminuria (EUA greater than 200 mg/l) in 7.5%. Cases with hypertension existing before or at onset of diabetes were 243 (HT group), cases without hypertension at onset were 371 (non HT group). In HT group, prevalence of microalbuminuria in increasing class of duration of diabetes were: 31% (0-4 years), 25% (5-9 years), 35% (10-14 years), 21% (15-19 years). Prevalence of macroalbuminuria was respectively: 3%, 11%, 15% and 4%. In the non HT group, microalbuminuria was present in 14% of the cases (0-4 years), 24% (5-9 years), 30% (10-14 years), 25% (15-19 years); prevalences of macroalbuminuria were: 1%, 8%, 6%, 15%. Mean values of UAE, compared to values of the class 0-2 years, were significantly higher in class 12-14 years (32.3 +/- 8 vs 14.4 +/- 3.7 mg/l; p = 0.02] in the HT group.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia.

    Science.gov (United States)

    Xu, Lili; Hu, Zhiyong; Shen, Jianjun; McQuillan, Patrick M

    2015-04-01

    Cerebral injury caused by hypoperfusion during the perioperative period is one of the main causes of disability and death in patients after major surgery. No effective protective or preventative strategies have been identified. This study was designed to evaluate the effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Sixty ASA (American Society of Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip replacement surgery, were enrolled in the study. They were randomly allocated to receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D group n=30) after induction of anesthesia. Blood samples were collected from radial artery and jugular venous bulb catheters for blood gas analysis and determination of glucose and lactate concentrations preoperatively, before surgical incision, at the end of surgery, and on post-op day 1. Arterial O2 content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated. There were no significant differences in CaO2 or Da-jvGlu during surgery between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at the end of surgery (T2) and on post-op day 1 (T3) than those in the control group (pGinkgo biloba extract can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and help maintain the balance between cerebral oxygen supply and consumption. It has no effect, however, on cerebral glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. A comparative study of the effects of methamphetamine on memory in existing and recovering addicts from a South African population

    Directory of Open Access Journals (Sweden)

    Cindy van Wyk

    2012-07-01

    Full Text Available Memory is a complex of systems by which an organism registers, stores and retrieves exposure toan event or experience. Literature purports that methamphetamine users and dependents havebeen found to exhibits signs of memory impairment. The aim of the research was to establishthe possible existence of significant differences in memory in current methamphetamine users,recovering methamphetamine users, and a matched drug naïve control group. Cognitivefunctioning was assessed via a neurocognitive test battery that examined the memory of14 current methamphetamine users, 17 recovering methamphetamine addicts, and 18 drugnaïve control participants who were matched according to the demographic variables of age,gender and educational status. The results indicated that recovering methamphetamine usersexperienced the greatest impairment in memory in comparison to both the control group andcurrent users of methamphetamine. The current users of methamphetamine also experiencedsome impairment in memory functioning in visual acquisition and retention. The poorperformance of the recovering addicts is explained by the juxtaposition of the stimulatingand supplemental effect of methamphetamine as experienced by the current users versus theneurotransmitter depletion and structural changes in the brain experienced by the recoveringaddicts. The control group showed a superior performance since they did not suffer from theneurotoxic effects of methamphetamine.

  7. A Population-based Longitudinal Study of Childhood Neurodevelopmental Disorders, IQ and Subsequent Risk of Psychotic Experiences in Adolescence

    Science.gov (United States)

    Khandaker, Golam M.; Stochl, Jan; Zammit, Stanley; Lewis, Glyn; Jones, Peter B

    2014-01-01

    Background Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (ND). Yet longitudinal studies of psychotic outcomes among individuals with ND are limited. We report a population-based prospective study of six common childhood ND, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence. Methods PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six neurodevelopmental disorders (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaire at age 9 years. Linear regression calculated mean difference in cognitive scores between those with and without ND. The association between ND and PEs was expressed as odds ratio (OR); effects of cognitive deficits were examined. Potential confounders included age, gender, father’s social class, ethnicity and maternal education. Results Out of 8,220 children, 487 (5.9%) were reported to have ND at age 9 years. Children with, compared with those without ND performed worse on all cognitive measures; adjusted mean difference in total IQ 6.84 (95% CI 5.00- 8.69). The association between total IQ and ND was linear (p<0.0001). The risk of PEs was higher in those with, compared with those without ND; adjusted OR for definite PEs 1.76 (95% CI 1.11- 2.79). IQ (but not working memory) deficit partly explained this association. Conclusion Higher risk of PEs in early adolescence among individuals with childhood ND is consistent with the neurodevelopmental hypothesis of schizophrenia. PMID:25066026

  8. Cognitive characterization of children with Dravet syndrome: A neurodevelopmental perspective.

    Science.gov (United States)

    Acha, Joana; Pérez, Alejandro; Davidson, Doug J; Carreiras, Manuel

    2015-01-01

    Dravet syndrome (DS) is an epilepsy of infantile onset, usually related to a mutation in gene sodium channel alpha 1 subunit, that leads to different typological seizures before the first year of life. Although most research has focused on the clinical description of the syndrome, some recent studies have focused on its impact on cognitive development, identifying both motor disorders and visual-processing deficits as basic factors affected in adults and children with DS. In this article, we designed a cross-sectional study to examine the cognitive phenotype of children affected by DS from a neurodevelopmental perspective. We report measures for both basic (auditory perception, visual and phonological processing, motor coordination) and higher order cognitive processes (verbal production, categorization, and executive function) in two age groups of DS children (M = 8.8 and M = 14.1) and control children of the same chronological age. Results showed an important cognitive delay in DS children with respect to controls in both basic and higher order cognitive abilities, with a better general outcome in tasks that required processing visual material (visual memory and categorization) than in tasks involving verbal material. In addition, performance of DS children in certain basic tasks (visual memory) correlated with performance on complex ones (categorization). These findings encourage promoting an early identification of not only clinical but also cognitive features in DS children from very early stages of development in order to optimize their neurodevelopmental outcome.

  9. Management of sleep disorders in neurodevelopmental disorders and genetic syndromes.

    Science.gov (United States)

    Heussler, Helen S

    2016-03-01

    Sleep disorders in individuals with developmental difficulties continue to be a significant challenge for families, carers, and therapists with a major impact on individuals and carers alike. This review is designed to update the reader on recent developments in this area. A systematic search identified a variety of studies illustrating advances in the regulation of circadian rhythm and sleep disturbance in neurodevelopmental disorders. Specific advances are likely to lead in some disorders to targeted therapies. There is strong evidence that behavioural and sleep hygiene measures should be first line therapy; however, studies are still limited in this area. Nonpharmacological measures such as exercise, sensory interventions, and behavioural are reported. Behavioural regulation and sleep hygiene demonstrate the best evidence for improved sleep parameters in individuals with neurodisability. Although the mainstay of management of children with sleep problems and neurodevelopmental disability is similar to that of typically developing children, there is emerging evidence of behavioural strategies being successful in large-scale trials and the promise of more targeted therapies for more specific resistant disorders.

  10. Effect of Co-existing Chronic Obstructive Pulmonary Disease and Cognitive Impairment on Health Outcomes in Older Adults

    Science.gov (United States)

    Chang, Sandy S.; Chen, Shu; McAvay, Gail J.; Tinetti, Mary E.

    2012-01-01

    Objectives To determine the extent to which the co-occurrence of chronic obstructive pulmonary disease (COPD) and cognitive impairment affect adverse health outcomes in older adults. Design Multi-center longitudinal cohort study. Setting California, Pennsylvania, Maryland, and North Carolina. Participants Three thousand ninety-three community-dwelling adults aged ≥65 from the Cardiovascular Health Study. Four hundred thirty-one participants had chronic obstructive pulmonary disease (COPD) at study baseline. Measurements Follow-up began at the second CHS visit and continued for three years. Spirometric criteria for airflow limitation served to establish COPD, using the Lambda-Mu-Sigma method, which accounts for age-related changes in lung function. Cognitive impairment was evaluated by the modified Mini Mental State Exam and claims data. Outcomes were respiratory-related and all-cause hospitalizations and death. Results Participants with co-existing COPD and cognitive impairment had the highest rates of respiratory-related (adjusted hazard ratio [HR]=4.10, 95%CI=1.86–9.05) and all-cause hospitalizations (HR= 1.34, 95%CI=1.00–1.80) and death (HR=2.29, 95%CI=1.18–4.45). In particular, individuals with both conditions had a 48% higher rate of all-cause hospitalizations (adjusted synergy index [SI]=1.48, 95%CI=0.19–11.31) and nearly a three-fold higher rate of death (SI=2.74, 95%CI=0.43–17.32) than the sum of risks for each respective outcome associated with having COPD or cognitive impairment alone. However, tests for interaction were not statistically significant for the presence of synergism between both conditions relative to any of the outcomes. Therefore, we cannot conclude that the combined effect of COPD and cognitive impairment is greater than additive. Conclusion Co-existing COPD and cognitive impairment have an additive effect on respiratory-related and all-cause hospitalizations and death. Optimizing outcomes in older adults with COPD and

  11. Cost-Effectiveness of HBV and HCV Screening Strategies – A Systematic Review of Existing Modelling Techniques

    Science.gov (United States)

    Geue, Claudia; Wu, Olivia; Xin, Yiqiao; Heggie, Robert; Hutchinson, Sharon; Martin, Natasha K.; Fenwick, Elisabeth; Goldberg, David

    2015-01-01

    Introduction Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers. PMID:26689908

  12. A population-based longitudinal study of childhood neurodevelopmental disorders, IQ and subsequent risk of psychotic experiences in adolescence.

    Science.gov (United States)

    Khandaker, G M; Stochl, J; Zammit, S; Lewis, G; Jones, P B

    2014-11-01

    Schizophrenia has a neurodevelopmental component to its origin, and may share overlapping pathogenic mechanisms with childhood neurodevelopmental disorders (NDs). Nevertheless, longitudinal studies of psychotic outcomes among individuals with NDs are limited. We report a population-based prospective study of six common childhood NDs, subsequent neurocognitive performance and the risk of psychotic experiences (PEs) in early adolescence. PEs were assessed by semi-structured interviews at age 13 years. IQ and working memory were measured between ages 9 and 11 years. The presence of six NDs (autism spectrum, dyslexia, dyspraxia, dysgraphia, dysorthographia, dyscalculia) was determined from parent-completed questionnaires at age 9 years. Linear regression calculated the mean difference in cognitive scores between children with and without NDs. Associations between NDs and PEs were expressed as odds ratios (ORs) with 95% confidence intervals (CIs); effects of cognitive deficits were examined. Potential confounders included age, gender, father's social class, ethnicity and maternal education. Out of 8220 children, 487 (5.9%) were reported to have NDs at age 9 years. Children with, compared with those without, NDs performed worse on all cognitive measures; the adjusted mean difference in total IQ was 6.84 (95% CI 5.00-8.69). The association between total IQ and NDs was linear (p memory) deficit partly explained this association. Higher risk of PEs in early adolescence among individuals with childhood ND is consistent with the neurodevelopmental hypothesis of schizophrenia.

  13. Neurodevelopmental Outcome in Children after Fetal Cardiac Intervention for Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome.

    Science.gov (United States)

    Laraja, Kristin; Sadhwani, Anjali; Tworetzky, Wayne; Marshall, Audrey C; Gauvreau, Kimberlee; Freud, Lindsay; Hass, Cara; Dunbar-Masterson, Carolyn; Ware, Janice; Lafranchi, Terra; Wilkins-Haug, Louise; Newburger, Jane W

    2017-05-01

    To characterize neurodevelopmental outcomes after fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome and determine the risk factors for adverse neurodevelopment. Questionnaires were mailed to families of children who underwent fetal aortic valvuloplasty from 2000 to 2012, and medical records were reviewed retrospectively. The primary outcome was the General Adaptive Composite score of the Adaptive Behavior Assessment System Questionnaire-Second Edition. Other questionnaires included the Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, and Pediatric Quality of Life Inventory. Among 69 eligible subjects, 52 (75%) completed questionnaires at median age of 5.5 (range 1.3-12) years; 30 (58%) had biventricular status circulation. The General Adaptive Composite mean score (92 ± 17) was lower than population norms (P Children, Behavior Rating Inventory of Executive Function, Ages and Stages, Pediatric Quality of Life Inventory), most subscale scores for patients with biventricular and single ventricular status were similar. Children who underwent fetal aortic valvuloplasty have neurodevelopmental delay, similar to patients with hypoplastic left heart syndrome without fetal intervention. Achievement of biventricular circulation was not associated with better outcomes. We infer that innate patient factors and morbidity during infancy have the greatest effect on neurodevelopmental outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Targeted treatments for cognitive and neurodevelopmental disorders in tuberous sclerosis complex.

    Science.gov (United States)

    de Vries, Petrus J

    2010-07-01

    Until recently, the neuropsychiatric phenotype of tuberous sclerosis complex (TSC) was presumed to be caused by the structural brain abnormalities and/or seizures seen in the disorder. However, advances in the molecular biology of the disorder have shown that TSC is a mammalian target of rapamycin (mTOR) overactivation syndrome, and that direct molecular pathways exist between gene mutation and cognitive/neurodevelopmental phenotype. Molecularly-targeted treatments using mTOR inhibitors (such as rapamycin) are showing great promise for the physical and neurological phenotype of TSC. Pre-clinical and early-phase clinical studies of the cognitive and neurodevelopmental features of TSC suggest that some of the neuropsychiatric phenotypes might also be reversible, even in adults with the disorder. TSC, fragile X, neurofibromatosis type 1, and disorders associated with phosphatase and tensin homo (PTEN) mutations, all signal through the mTOR signaling pathway, with the TSC1-TSC2 protein complex as a molecular switchboard at its center. Together, these disorders represent as much as 14% of autism spectrum disorders (ASD). Therefore, we suggest that this signaling pathway is a key to the underlying pathophysiology of a significant subset of individuals with ASD. The study of molecularly targeted treatments in TSC and related disorders, therefore, may be of scientific and clinical value not only to those with TSC, but to a larger population that may have a neuropsychiatric phenotype attributable to mTOR overactivation or dysregulation. (c) 2010 The American Society for Experimental NeuroTherapeutics, Inc. Published by Elsevier Inc. All rights reserved.

  15. Thyroid hormones for preventing neurodevelopmental impairment in preterm infants.

    Science.gov (United States)

    Osborn, D A

    2001-01-01

    Observational studies have shown an association between transiently low thyroid hormone levels in preterm infants in the first weeks of life (transient hypothyroxinemia) and abnormal neurodevelopmental outcome. Thyroid hormone therapy might prevent this morbidity. To assess whether thyroid hormone therapy in preterm infants without congenital hypothyroidism results in clinically important changes in neonatal and long term outcomes in terms of benefits and harms. The standard search strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching in the English language. All trials using random or quasi-random patient allocation, in which thyroid hormone therapy (either treatment or prophylaxis) was compared to control in premature infants. Primary clinical outcomes included measures of neurodevelopmental outcome and mortality. Assessment of trial quality, data extraction and synthesis of data, using relative risk (RR) and weighted mean difference (WMD), were performed using standard methods of the Cochrane Collaboration and its Neonatal Review Group. Nine studies were identified that compared thyroid hormone treatment to control. Four randomized and one quasi-randomized study met inclusion criteria. All studies enrolled preterm infants thyroid hormones. Four studies used thyroxine, whereas Amato 1989 used triiodothyronine. Only two studies with neurodevelopmental follow-up were of good methodology. All studies were of small size with the largest, van Wassenaer 1997, enrolling 200 infants. Meta-analysis of five studies found no significant difference in mortality to discharge (typical RR 0.70, 95% CI 0.42, 1.17) in infants who received thyroid hormone treatment compared to controls. Meta-analysis of two studies found no significant

  16. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial.

    Science.gov (United States)

    Davidson, Andrew J; Disma, Nicola; de Graaff, Jurgen C; Withington, Davinia E; Dorris, Liam; Bell, Graham; Stargatt, Robyn; Bellinger, David C; Schuster, Tibor; Arnup, Sarah J; Hardy, Pollyanna; Hunt, Rodney W; Takagi, Michael J; Giribaldi, Gaia; Hartmann, Penelope L; Salvo, Ida; Morton, Neil S; von Ungern Sternberg, Britta S; Locatelli, Bruno Guido; Wilton, Niall; Lynn, Anne; Thomas, Joss J; Polaner, David; Bagshaw, Oliver; Szmuk, Peter; Absalom, Anthony R; Frawley, Geoff; Berde, Charles; Ormond, Gillian D; Marmor, Jacki; McCann, Mary Ellen

    2016-01-16

    Preclinical data suggest that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia can have an increased risk of poor neurodevelopmental outcome. We aimed to establish whether general anaesthesia in infancy has any effect on neurodevelopmental outcome. Here we report the secondary outcome of neurodevelopmental outcome at 2 years of age in the General Anaesthesia compared to Spinal anaesthesia (GAS) trial. In this international assessor-masked randomised controlled equivalence trial, we recruited infants younger than 60 weeks postmenstrual age, born at greater than 26 weeks' gestation, and who had inguinal herniorrhaphy, from 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand. Infants were randomly assigned (1:1) to receive either awake-regional anaesthesia or sevoflurane-based general anaesthesia. Web-based randomisation was done in blocks of two or four and stratified by site and gestational age at birth. Infants were excluded if they had existing risk factors for neurological injury. The primary outcome of the trial will be the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) Full Scale Intelligence Quotient score at age 5 years. The secondary outcome, reported here, is the composite cognitive score of the Bayley Scales of Infant and Toddler Development III, assessed at 2 years. The analysis was as per protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. This trial is registered with ANZCTR, number ACTRN12606000441516 and ClinicalTrials.gov, number NCT00756600. Between Feb 9, 2007, and Jan 31, 2013, 363 infants were randomly assigned to receive awake-regional anaesthesia and 359 to general anaesthesia. Outcome data were available for 238 children in the awake-regional group and 294 in the general anaesthesia group. In the

  17. The effect of extremity strength training on fibromyalgia symptoms and disease impact in an existing multidisciplinary treatment program.

    Science.gov (United States)

    Kas, Tamara; Colby, Megan; Case, Maureen; Vaughn, Dan

    2016-10-01

    The purpose of this study was to examine the effect of upper and lower body extremity strengthening exercise in patients with Fibromyalgia (FM) within an existing multidisciplinary treatment program. Patients between the ages of 18-65 with the medical diagnosis of FM. Comparative study design. The control and experimental group received the same multidisciplinary treatment except that the experimental group performed upper and lower extremity strengthening exercises. The Fibromyalgia Impact Questionnaire (FIQ) was administered at evaluation and discharge from the program in order to measure change in quality of life (QOL). Statistically significant changes in FIQ scores were found for both groups. The addition of extremity strengthening in the experimental group produced an average 4 points greater reduction in FIQ score, however, these results are not considered statistically significant. This study appears to validate the success of a multidisciplinary approach in treating patients with FM, with the possibility for further benefit with the addition of extremity strengthening. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Schatzki's Ring in Angelman Syndrome: A Diagnostic Dilemma in Neurodevelopmentally Disabled Patients

    OpenAIRE

    Choi, Young Sammy; Sachar, David Scott

    2009-01-01

    Angelman Syndrome is a neurodevelopmental condition with a characteristic phenotype that includes epilepsy and lack of communication. We describe its first reported association with Schatzki's ring that presented as a life-long history of intermittent retching. Because of associated cognitive dysfunction, careful diagnostic consideration is required to detect this underlying condition. Keywords Schatzki's ring; Angelman Syndrome; Esophageal "B" ring; Barium esophagogram; Neurodevelopmental de...

  19. Piece Work: Fabric Collage as a Neurodevelopmental Approach to Trauma Treatment

    Science.gov (United States)

    Homer, Eliza S.

    2015-01-01

    This article describes the use of collaborative fabric collage based on a neurodevelopmental adaptation for an adult who was being treated for trauma. The case demonstrates the value of thinking about neurodevelopmental factors when creating art therapy interventions. A biologically respectful treatment that offers relational, relevant,…

  20. Twin-twin transfusion syndrome: neurodevelopmental screening test

    Directory of Open Access Journals (Sweden)

    Amabile Vessoni Arias

    2015-03-01

    Full Text Available Objective To assess the neurodevelopmental functions (cognition, language and motor function of survivors of twin-twin transfusion syndrome (TTTS. Method Observational cross-sectional study of a total of 67 monochorionic diamniotic twins who underwent fetoscopic laser coagulation (FLC for treatment of TTTS. The study was conducted at the Center for Investigation in Pediatrics (CIPED, Universidade Estadual de Campinas. Ages ranged from one month and four days to two years four months. Bayley Scales of Infant and Toddler Development Screening Test-III, were used for evaluation. Results Most children reached the competent category and were classified as having appropriate performance. The preterm children scored worse than term infants for gross motor subtest (p = 0.036. Conclusion The majority of children reached the expected development according to their age. Despite the good neurodevelopment, children classified at risk should be monitored for development throughout childhood.

  1. The genetic relationship between handedness and neurodevelopmental disorders☆

    Science.gov (United States)

    Brandler, William M.; Paracchini, Silvia

    2014-01-01

    Handedness and brain asymmetry have been linked to neurodevelopmental disorders such as dyslexia and schizophrenia. The genetic nature of this correlation is not understood. Recent discoveries have shown handedness is determined in part by the biological pathways that establish left/right (LR) body asymmetry during development. Cilia play a key role in this process, and candidate genes for dyslexia have also been recently shown to be involved in cilia formation. Defective cilia result not only in LR body asymmetry phenotypes but also brain midline phenotypes such as an absent corpus callosum. These findings suggest that the mechanisms for establishing LR asymmetry in the body are reused for brain midline development, which in turn influences traits such as handedness and reading ability. PMID:24275328

  2. Angelman Syndrome: Insights into Genomic Imprinting and Neurodevelopmental Phenotypes

    Science.gov (United States)

    Mabb, Angela M.; Judson, Matthew C.; Zylka, Mark J.; Philpot, Benjamin D.

    2011-01-01

    Angelman syndrome (AS) is a severe genetic disorder caused by mutations or deletions of the maternally inherited UBE3A gene. UBE3A encodes an E3 ubiquitin ligase that is expressed biallelically in most tissues but is maternally expressed in almost all neurons. In this review, we describe recent advances in understanding the expression and function of UBE3A in the brain and the etiology of AS. We highlight current AS model systems, epigenetic mechanisms of UBE3A regulation, and the identification of potential UBE3A substrates in the brain. In the process, we identify major gaps in our knowledge that, if bridged, could move us closer to identifying treatments for this debilitating neurodevelopmental disorder. PMID:21592595

  3. Behavioral Phenotyping Assays for Genetic Mouse Models of Neurodevelopmental, Neurodegenerative, and Psychiatric Disorders.

    Science.gov (United States)

    Sukoff Rizzo, Stacey J; Crawley, Jacqueline N

    2017-02-08

    Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent behavioral symptoms. Mouse behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse behavioral tests available in the established behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategies can be employed to test hypotheses about environmental causes and gene × environment interactions.

  4. Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes.

    Science.gov (United States)

    Furlong, Melissa A; Herring, Amy; Buckley, Jessie P; Goldman, Barbara D; Daniels, Julie L; Engel, Lawrence S; Wolff, Mary S; Chen, Jia; Wetmur, Jim; Barr, Dana Boyd; Engel, Stephanie M

    2017-10-01

    Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6-9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores (β^ - 0.13, 95% CI - 0.26, 0.00) but positively associated with Executive Functioning factor scores (β^ 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index (β^ - 0.17, 95% CI - 0.33, - 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Neurodevelopmental profile in Angelman syndrome: more than low intelligence quotient.

    Science.gov (United States)

    Micheletti, S; Palestra, F; Martelli, P; Accorsi, P; Galli, J; Giordano, L; Trebeschi, V; Fazzi, E

    2016-10-21

    Angelman Syndrome (AS) is a rare neurodevelopment disorder resulting from deficient expression or function of the maternally inherited allele of UBE3A gene. The aim of the study is to attempt at providing a detailed definition of neurodevelopmental profile in AS, with particular regard to motor, cognitive, communicative, behavioural and neurovisual, features by using standardized instruments. A total of ten subjects aged from 5 to 11 years (4 males and 6 females) with molecular confirmed diagnosis of AS (7 15q11.2-q13 deletion and 3 UBE3A mutation) were enrolled in our study. All of them underwent an assessment protocol including neurological and neurovisual examination and the evaluation of motor (Gross Motor Function Measure Scale), cognitive (Griffiths Mental Development Scale and Uzgiris-Hunt Scale); adaptive (Vineland Adaptive Behavioural Scale); communication (MacArthur-Bates Communicative Development Inventory and video-recordings children's verbal expression), behavioural aspects (IPDDAG Scale) and neurovisual aspects. All children presented motor function involvement. A severe cognitive impairment was detected with different profiles according to the test applied. In all cases, communicative disability (phonemic inventory, word/gesture comprehension and production) and symptoms of inattention disorder were revealed. Neurovisual impairment was characterized by refractive errors, fundus oculi anomalies, strabismus and/or oculomotor dysfunction. AS presents a complex neurodevelopmental profile in which several aspects play a negative role in global development leading to a severe functional impairment. Intellectual disability is not the only component because neurovisual functions and behavioural disorders may worsen the global function and are needed of specific rehabilitation programs.

  6. Neurodevelopmental outcome of 31 patients with borderline fetal ventriculomegaly.

    Science.gov (United States)

    Tatlı, Burak; Özer, Irmak; Ekici, Barış; Kalelioğlu, Ibrahim; Has, Recep; Eraslan, Emine; Yüksel, Atıl

    2012-09-01

    We present the neurodevelopmental outcome of patients with isolated borderline fetal ventriculomegaly. The present study was carried out at the Department of Pediatric Neurology, Istanbul Medical Faculty, Istanbul University in July-December 2010. Prenatal second trimester detailed ultrasound examinations were performed by obstetricians at the Prenatal Diagnosis Department of Istanbul Medical School, and 31 consecutive patients aged 8-33 months have been included in the study. Four patients with atrial diameters of over 15 mm and three patients with central nervous system development anomalies were excluded from the study. In order to assess the neuromotor development of patients, neurologic examinations and the Bayley Scales of Infant Development (BSID-III) were used. Nine patients were female (29%) and 22 were male (71%). In the postnatal period, tuberous sclerosis was found in one patient, Down syndrome in one, and equinovarus foot deformity in one. Atrial diameter was patients and >12 mm in 13. Cranial ultrasounds done in the first postnatal month revealed persisting ventriculomegaly in nine patients. The two patients who scored significantly low in all areas on the Bayley Scales of Infant Development were the patients with Down syndrome and tuberous sclerosis. The one scoring low in the motor area was the patient with the equinovarus foot deformity. The BSID-III scores of the patients whose prenatal ventricle diameter was patients showing slight developmental delay were the ones whose cranial ultrasound in the first postnatal month showed persisting ventriculomegaly. In patients with borderline fetal ventriculomegaly, atrial diameter being more than 12 mm, the condition persisting in the first postnatal month and the presence of accompanying syndromes and malformations all constitute clear risk factors for neurodevelopmental outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Markers of neurodevelopmental impairments in early-onset psychosis

    Directory of Open Access Journals (Sweden)

    Petruzzelli MG

    2015-07-01

    Full Text Available Maria Giuseppina Petruzzelli,1 Lucia Margari,1 Francesco Craig,1 Maria Gloria Campa,1 Domenico Martinelli,2 Adriana Pastore,3 Marta Simone,1 Francesco Margari3 1Child and Adolescence Neuropsychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University “Aldo Moro” of Bari, 2Department of Medical and Surgical Sciences; University of Foggia, Foggia, 3Psychiatry Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organ, University “Aldo Moro” of Bari, Bari, Italy Background: The aim of this study was to assess the association between the clinical and neurobiological markers of neurodevelopmental impairments and early-onset schizophrenia spectrum psychosis. Methods: A sample of 36 patients with early-onset schizophrenia spectrum psychosis was compared to a control sample of 36 patients with migraine. We assessed early childhood neurodevelopmental milestones using a modified version of the General Developmental Scale, general intellectual ability using the Wechsler Intelligence Scale for Children–Revised or Leiter International Performance Scale–Revised for patients with speech and language abnormalities, and neurological soft signs with specific regard to subtle motor impairment. Results: Subjects with early-onset psychosis had a higher rate of impaired social development (P=0.001, learning difficulties (P=0.04, enuresis (P=0.0008, a lower intelligence quotient (P<0.001, and subtle motor impairments (P=0.005 than control subjects. Conclusion: We suggest that neurodevelopment in early-onset psychosis is characterized by a global impairment of functional and adaptive skills that manifests from early childhood, rather than a delay or limitation in language and motor development. The current evidence is based on a small sample and should be investigated in larger samples in future research. Keywords: early-onset psychosis, early-onset schizophrenia, neurodevelopment, social cognition

  8. Neurodevelopmental Outcomes of Extremely Preterm Infants Randomized to Stress Dose Hydrocortisone.

    Directory of Open Access Journals (Sweden)

    Nehal A Parikh

    Full Text Available To compare the effects of stress dose hydrocortisone therapy with placebo on survival without neurodevelopmental impairments in high-risk preterm infants.We recruited 64 extremely low birth weight (birth weight ≤1000 g infants between the ages of 10 and 21 postnatal days who were ventilator-dependent and at high-risk for bronchopulmonary dysplasia. Infants were randomized to a tapering 7-day course of stress dose hydrocortisone or saline placebo. The primary outcome at follow-up was a composite of death, cognitive or language delay, cerebral palsy, severe hearing loss, or bilateral blindness at a corrected age of 18-22 months. Secondary outcomes included continued use of respiratory therapies and somatic growth.Fifty-seven infants had adequate data for the primary outcome. Of the 28 infants randomized to hydrocortisone, 19 (68% died or survived with impairment compared with 22 of the 29 infants (76% assigned to placebo (relative risk: 0.83; 95% CI, 0.61 to 1.14. The rates of death for those in the hydrocortisone and placebo groups were 31% and 41%, respectively (P = 0.42. Randomization to hydrocortisone also did not significantly affect the frequency of supplemental oxygen use, positive airway pressure support, or need for respiratory medications.In high-risk extremely low birth weight infants, stress dose hydrocortisone therapy after 10 days of age had no statistically significant effect on the incidence of death or neurodevelopmental impairment at 18-22 months. These results may inform the design and conduct of future clinical trials.ClinicalTrials.gov NCT00167544.

  9. Pathfinder to EXIST: ProtoEXIST

    Science.gov (United States)

    Garson, A. B., III; Allen, B.; Baker, R. G.; Barthelmy, S. D.; Burke, M.; Burnham, J.; Chammas, N.; Collins, J.; Cook, W. R.; Copete, A.; Gehrels, N.; Gauron, T.; Grindlay, J.; Harrison, F. A.; Hong, J.; Howell, J.; Krawczynski, H.; Labov, S.; Said, B.; Sheikh Sheikh, S.

    2008-04-01

    We describe the ProtoEXIST instrument, our fist-generation wide-field hard X-ray imaging (20 - 600 keV) balloon-borne telescope. The ProtoEXIST program is a pathfinder for the Energetic X-ray Imaging Survey Telescope (EXIST), a candidate for the Black Hole Finder Probe. ProtoEXIST consists of two independent coded-aperture telescopes using pixellated (2.5mm pitch) CZT detectors. The two telescopes will provide performance comparison of two shielding configurations, for optimization of the EXIST design. We report on the science goals and designs of both ProtoEXIST and EXIST and their implications for hard X-ray astronomy and astrophysics.

  10. The (in)existence of legal aid in the administrative arbitration: the right of access jurisdictional effective trusteeship?

    OpenAIRE

    Preto, Ana Cristina Castro Felgueiras

    2014-01-01

    Dissertação de mestrado em Direito Administrativo A (in)existência de Apoio Judiciário na Arbitragem Administrativa: o Direito de Acesso à Tutela Jurisdicional Efetiva? Este trabalho resume-se à consciencialização de que o fenómeno da desjudicialização da justiça, operada pelos ADR, e em concreto a arbitragem administrativa, é apontada como um fator de numerosas vantagens. A arbitragem é um meio jurisdicional de resolução de litígios, com uma existência milenar e que, atu...

  11. Neurodevelopmental effects of prenatal exposure to psychotropic medications.

    Science.gov (United States)

    Gentile, Salvatore

    2010-07-01

    Until now, studies on the reproductive safety of psychotropics have typically assessed the risk of congenital malformations and perinatal complications associated with in utero exposure to such medications. However, little is known of their inherent potential neurobehavioral teratogenicity. The objective is to analyze available data from studies investigating developmental outcome of children exposed prenatally to psychotropics. A computerized Medline/PubMed/TOXNET/ENBASE search (1960-2010) was conducted using the following keywords: pregnancy, child/infant development/neurodevelopment, antidepressants, benzodiazepines, mood stabilizers, and antipsychotics. A separate search was also run to complete the safety profile of single specific medications. Resultant articles were cross-referenced for other relevant articles not identified in the initial search. A noncomputerized review of pertinent journals and textbooks was also performed. All studies published in English and reporting primary data on the developmental outcome of infants exposed in utero to psychotropics and born without malformations were collected. As regards antiepileptic drugs, only studies that provided data on specific medications approved for psychiatric practice use (carbamazepine, lamotrigine, and valproate) were considered. Data were extracted from 41 articles (38 identified electronically and 3 nonelectronically), which met the inclusion criteria. Despite reviewed studies showing relevant methodological limitations, concordant, albeit preliminary, information seems to exclude that prenatal exposure to both selective serotonin reuptake inhibitors and tricyclic antidepressants may interfere with the infants' psychological and cognitive development. Conversely, information on valproate strongly discourages its use in pregnant women. Moreover, although data on carbamazepine remain controversial, information on whole classes of drugs and single medications is either absent (second-generation antipsychotics) or too limited (first-generation antipsychotics, benzodiazepines, lithium, and lamotrigine) to inform the decision-making process. For all classes of psychotropics, new and/or further studies are warranted to answer definitively the urgent question about the impact of prenatal exposure to such medications on infant development. 2010 Wiley-Liss, Inc.

  12. Neurodevelopmental effects of insulin-like growth factor signaling

    Science.gov (United States)

    O’Kusky, John; Ye, Ping

    2012-01-01

    Insulin-like growth factor (IGF) signaling greatly impacts the development and growth of the central nervous system (CNS). IGF-I and IGF-II, two ligands of the IGF system, exert a wide variety of actions both during development and in adulthood, promoting the survival and proliferation of neural cells. The IGFs also influence the growth and maturation of neural cells, augmenting dendritic growth and spine formation, axon outgrowth, synaptogenesis, and myelination. Specific IGF actions, however, likely depend on cell type, developmental stage, and local microenvironmental milieu within the brain. Emerging research also indicates that alterations in IGF signaling likely contribute to the pathogenesis of some neurological disorders. This review summarizes experimental studies and shed light on the critical roles of IGF signaling, as well as its mechanisms, during CNS development. PMID:22710100

  13. Combined effects of axial load and concrete strength variation on the seismic performance of existing RC buildings

    NARCIS (Netherlands)

    Mariani, V.; Tanganelli, Marco; Viti, Stefania; De Stefano, M.

    2016-01-01

    It is well known that the axial load plays an important role in the evaluation of the structural capacity of RC columns. In existing buildings this problem can be even more significant than in new ones, since the material can easily present poor mechanical properties. The paper is aimed at the

  14. The effect of pre-existing immunity on the capacity of influenza virosomes to induce cytotoxic T lymphocyte activity

    NARCIS (Netherlands)

    de Mare, Arjan; Bungener, Laura B.; Regts, Joke; de Vries-Idema, Jacqueline; van der Zee, Ate G. J.; Witschut, Jan; Daemen, Toos

    2008-01-01

    Protein antigens encapsulated in virosomes generated from influenza virus can induce antigen-specific cytotoxic T lymphocyte (CTL) responses. In the present study we determined, in a murine model system, whether pre-existing immunity against influenza virus hampers the induction of a CTL response.

  15. Can a safety-in-numbers effect and a hazard-in-numbers effect co-exist in the same data?

    Science.gov (United States)

    Elvik, Rune

    2013-11-01

    Safety-in-numbers denotes a non-linear relationship between exposure (traffic volume) and the number of accidents, characterised by declining risk as traffic volume increases. There is safety-in-numbers when the number of accidents increases less than proportional to traffic volume, e.g. a doubling of traffic volume is associated with less than a doubling of the number of accidents. Hazard-in-numbers, a less-used concept, refers to the opposite effect: the number of accidents increases more than in proportion to traffic volume, e.g. is more than doubled when traffic volume is doubled. This paper discusses whether a safety-in-numbers effect and a hazard-in-numbers effect can co-exist in the same data. It is concluded that both effects can exist in a given data set. The paper proposes to make a distinction between partial safety-in-numbers and complete safety-in-numbers. Another issue that has been raised in discussions about the safety-in-numbers effect is whether the effect found in some studies is an artefact created by the way exposure was measured. The paper discusses whether measuring exposure as a rate or a share, e.g. kilometres travelled per inhabitant per year, will generate a safety-in-numbers effect as a statistical artefact. It is concluded that this is the case. The preferred measure of exposure is a count of the number of road users. The count should not be converted to a rate or to the share any group of road user contribute to total traffic volume. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Background Studies for EXIST

    Science.gov (United States)

    Wilson, Colleen A.; Pendleton, G. N.; Fishman, G. J.

    2004-01-01

    We present results from a study of the trapped proton and electron background for several orbital inclinations and altitudes. This study includes time dependent effects. In addition we describe a 3 component cosmic background model developed at the University of Southampton, UK. The three components are cosmic diffuse gamma rays, atmospheric albedo gamma rays, and cosmic ray protons. We present examples of how this model was applied to BATSE and discuss its application to EXIST.

  17. Targeting neural synchrony deficits is sufficient to improve cognition in a schizophrenia-related neurodevelopmental model

    Directory of Open Access Journals (Sweden)

    Heekyung eLee

    2014-02-01

    Full Text Available Cognitive symptoms are core features of mental disorders but procognitive treatments are limited. We have proposed a ‘discoordination’ hypothesis that cognitive impairment results from aberrant coordination of neural activity. We reported that neonatal ventral hippocampus lesion (NVHL rats, an established neurodevelopmental model of schizophrenia, have abnormal neural synchrony and cognitive deficits in the active place avoidance task. During stillness, we observed that cortical local field potentials sometimes resembled epileptiform spike-wave discharges with higher prevalence in NVHL rats, indicating abnormal neural synchrony due perhaps to imbalanced excitation-inhibition coupling. Here, within the context of the hypothesis, we investigated whether attenuating abnormal neural synchrony will improve cognition in NVHL rats. We report that 1 interhippocampal synchrony in the theta and beta bands is correlated with active place avoidance performance; 2 the anticonvulsant ethosuximide attenuated the abnormal spike-wave activity, improved cognitive control, and reduced hyperlocomotion; 3 ethosuximide normalized the task-associated theta and beta synchrony between the two hippocampi but also increased synchrony between the medial prefrontal cortex and hippocampus above control levels; 4 the antipsychotic olanzapine was less effective at improving cognitive control and normalizing place avoidance-related inter-hippocampal neural synchrony, although it reduced hyperactivity; and 5 olanzapine caused an abnormal pattern of frequency-independent increases in neural synchrony, in both NVHL and control rats. These data suggest that normalizing aberrant neural synchrony can be beneficial and that drugs targeting the pathophysiology of abnormally coordinated neural activities may be a promising theoretical framework and strategy for developing treatments that improve cognition in neurodevelopmental disorders such as schizophrenia.

  18. Neurodevelopmental disorders are highly over-represented in children with obesity: A cross-sectional study.

    Science.gov (United States)

    Wentz, Elisabet; Björk, Anna; Dahlgren, Jovanna

    2017-01-01

    To investigate prevalence of neurodevelopmental disorders in children with obesity and to compare body mass index (BMI) and metabolic profile in the children. Seventy-six children (37 girls, 39 boys) were consecutively recruited from a university outpatient clinic specialized in severe obesity. Neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD) were assessed using interviews and questionnaires. Neurodevelopmental diagnoses were collected retrospectively in medical records. BMI ranged between 1.9 and 5.9 SDS and age between 5.1 and 16.5 years. In 13.2% and 18.4% ASD and ADHD was assigned, respectively. In addition, 25% screened positive for DCD, 31.6% had at least one neurodevelopmental disorder, and 18.4% had a parent who screened positive for adult ADHD. Girls with ASD/ADHD had higher BMI SDS than girls without neurodevelopmental disorder (P = 0.006). One third of children with obesity referred to specialist centers have a neurodevelopmental disorder including deviant motor skills, and these problems may deteriorate weight status. One fifth of the parents exhibit ADHD symptomatology which could partly explain the poor adherence by some families in obesity units. Future obesity therapy could benefit from incorporating a neurodevelopmental treatment approach. © 2016 The Obesity Society.

  19. EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy.

    Science.gov (United States)

    Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G W; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana; Flanigan, Kevin M; Manickam, Kandamurugu; Zmuda, Erik; Banks, Wesley; Gershoni-Baruch, Ruth; Mandel, Hanna; Dagan, Efrat; Raas-Rothschild, Annick; Barash, Hila; Filloux, Francis; Creel, Donnell; Harris, Michael; Hamosh, Ada; Kölker, Stefan; Ebrahimi-Fakhari, Darius; Hoffmann, Georg F; Manchester, David; Boyer, Philip J; Manzur, Adnan Y; Lourenco, Charles Marques; Pilz, Daniela T; Kamath, Arveen; Prabhakar, Prab; Rao, Vamshi K; Rogers, R Curtis; Ryan, Monique M; Brown, Natasha J; McLean, Catriona A; Said, Edith; Schara, Ulrike; Stein, Anja; Sewry, Caroline; Travan, Laura; Wijburg, Frits A; Zenker, Martin; Mohammed, Shehla; Fanto, Manolis; Gautel, Mathias; Jungbluth, Heinz

    2016-03-01

    Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0-49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed

  20. The pre-existing population of 5S rRNA effects p53 stabilization during ribosome biogenesis inhibition.

    Science.gov (United States)

    Onofrillo, Carmine; Galbiati, Alice; Montanaro, Lorenzo; Derenzini, Massimo

    2017-01-17

    Pre-ribosomal complex RPL5/RPL11/5S rRNA (5S RNP) is considered the central MDM2 inhibitory complex that control p53 stabilization during ribosome biogenesis inhibition. Despite its role is well defined, the dynamic of 5S RNP assembly still requires further characterization. In the present work, we report that MDM2 inhibition is dependent by a pre-existing population of 5S rRNA.

  1. National-level infrastructure and economic effects of switchgrass cofiring with coal in existing power plants for carbon mitigation.

    Science.gov (United States)

    Morrow, William R; Griffin, W Michael; Matthews, H Scott

    2008-05-15

    We update a previously presented Linear Programming (LP) methodology for estimating state level costs for reducing CO2 emissions from existing coal-fired power plants by cofiring switchgrass, a biomass energy crop, and coal. This paper presents national level results of applying the methodology to the entire portion of the United States in which switchgrass could be grown without irrigation. We present incremental switchgrass and coal cofiring carbon cost of mitigation curves along with a presentation of regionally specific cofiring economics and policy issues. The results show that cofiring 189 million dry short tons of switchgrass with coal in the existing U.S. coal-fired electricity generation fleet can mitigate approximately 256 million short tons of carbon-dioxide (CO2) per year, representing a 9% reduction of 2005 electricity sector CO2 emissions. Total marginal costs, including capital, labor, feedstock, and transportation, range from $20 to $86/ton CO2 mitigated,with average costs ranging from $20 to $45/ton. If some existing power plants upgrade to boilers designed for combusting switchgrass, an additional 54 million tons of switchgrass can be cofired. In this case, total marginal costs range from $26 to $100/ton CO2 mitigated, with average costs ranging from $20 to $60/ton. Costs for states east of the Mississippi River are largely unaffected by boiler replacement; Atlantic seaboard states represent the lowest cofiring cost of carbon mitigation. The central plains states west of the Mississippi River are most affected by the boiler replacement option and, in general, go from one of the lowest cofiring cost of carbon mitigation regions to the highest. We explain the variation in transportation expenses and highlight regional cost of mitigation variations as transportation overwhelms other cofiring costs.

  2. Subtle bilirubin-induced neurodevelopmental dysfunction (BIND) in the term and late preterm infant : Does it exist?

    NARCIS (Netherlands)

    Lunsing, Roelineke J.

    2014-01-01

    Subtle bilirubin-induced neurological dysfunction (BIND) is defined as disturbances in sensory and sensorimotor integration, central auditory processing, coordination, and muscle tone in the absence of the classical findings of kernicterus. This review is restricted to the (sensori)motor signs of

  3. Genetic and Environmental Control of Neurodevelopmental Robustness in Drosophila.

    Directory of Open Access Journals (Sweden)

    David J Mellert

    Full Text Available Interindividual differences in neuronal wiring may contribute to behavioral individuality and affect susceptibility to neurological disorders. To investigate the causes and potential consequences of wiring variation in Drosophila melanogaster, we focused on a hemilineage of ventral nerve cord interneurons that exhibits morphological variability. We find that late-born subclasses of the 12A hemilineage are highly sensitive to genetic and environmental variation. Neurons in the second thoracic segment are particularly variable with regard to two developmental decisions, whereas its segmental homologs are more robust. This variability "hotspot" depends on Ultrabithorax expression in the 12A neurons, indicating variability is cell-intrinsic and under genetic control. 12A development is more variable and sensitive to temperature in long-established laboratory strains than in strains recently derived from the wild. Strains with a high frequency of one of the 12A variants also showed a high frequency of animals with delayed spontaneous flight initiation, whereas other wing-related behaviors did not show such a correlation and were thus not overtly affected by 12A variation. These results show that neurodevelopmental robustness is variable and under genetic control in Drosophila and suggest that the fly may serve as a model for identifying conserved gene pathways that stabilize wiring in stressful developmental environments. Moreover, some neuronal lineages are variation hotspots and thus may be more amenable to evolutionary change.

  4. Neurodevelopmental outcome in Angelman syndrome: genotype-phenotype correlations.

    Science.gov (United States)

    Mertz, Line Granild Bie; Thaulov, Per; Trillingsgaard, Anegen; Christensen, Rikke; Vogel, Ida; Hertz, Jens Michael; Ostergaard, John R

    2014-07-01

    Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, developmental delay, lack of speech, and epileptic seizures. Previous studies have indicated that children with AS due to 15q11.2-q13 deletions have a more severe developmental delay and present more often autistic features than those with AS caused by other genetic etiologies. The present study investigated the neurodevelopmental profiles of the different genetic etiologies of AS, and examined the evolution of mental development and autistic features over a 12-year period in children with a 15q11.2-q13 deletion. This study included 42 children with AS. Twelve had a Class I deletion, 18 had Class II deletions, three showed atypical large deletions, five had paternal uniparental disomy (pUPD) and four had UBE3A mutations. Children with a deletion (Class I and Class II) showed significantly reduced developmental age in terms of visual perception, receptive language, and expressive language when compared to those with a UBE3A mutation and pUPD. Within all subgroups, expressive language performance was significantly reduced when compared to the receptive performance. A follow-up study of seven AS cases with 15q11.2-q13 deletions revealed that over 12 years, the level of autistic features did not change, but both receptive and expressive language skills improved. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. NEURODEVELOPMENTAL CARE OF PRETERM BABIES AND ITS KEY ELEMENTS

    Directory of Open Access Journals (Sweden)

    I. M. Sarapuk

    2017-07-01

    Full Text Available Over the past few decades, the advancements in the perinatal and neonatal intensive care have led to a significant survival of premature infants. However neurodevelopmental outcome still remains the topical issues of concern. Developmental care is an approach that is aimed to reduce the mismatches between extra- and intra-uterine environments, decrease the stress of preterm newborns in neonative intensive care units, and thus promote optimal neurobehavioral development of the infant. The Newborn Individualized Developmental Care and Assessment Program (NIDCAP model was developed as a clinical framework for the implementation of developmental care. The model focuses on detailed reading of each individual infant’s behavioral cues. By observing the child during the routine manipulation performance (before, during and after and a detailed description of his/her behavioral responses, a professional can assess the ability of the infant’s immature nervous system to tolerate the environment and care manipulations. Such evaluation will enable to determine the adequacy of environmental conditions and care manipulations to baby’s opportunities and needs, with their subsequent correction and adaptation. NIDCAP’s aim is to support the child in its increasing tolerance to stimuli and to minimize stressful events and manipulation. With the help of NIDCAP approaches in neonatal care, medical staff study how to read infants’ behavior, hear their voice and understand them.

  6. Neurodevelopmental profile of Down syndrome in Chinese children.

    Science.gov (United States)

    Kwong, K L; Wong, V

    1996-04-01

    To give an overall appraisal of the clinical features of Down syndrome (DS) in Chinese children with emphasis on the neurodevelopmental outcome, and to compare the related complications with that of other races. The records of 124 Chinese children with DS assessed at the Child Assessment Centre of the University Department of Paediatrics in the Duchess of Kent Children's Hospital from 1985 to 1993 were reviewed. Thirty-one per cent of patients had microcephaly. Eighty-five percent (33/39) when assessed in the first year of life had a developmental quotient (DQ) above 50 but only 29% (2/7) had DQ above 50 when assessed after the age of 5. Only two patients (1.6%) had epilepsy: infantile spasms (1) and Lennox-Gastaut syndrome (1). Hearing impairment was found in 45% of children with mild conductive hearing impairment being the most common. Chinese children with DS, when compared with other races, were similarly intellectually disabled, but were less likely to develop epilepsy.

  7. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

    Directory of Open Access Journals (Sweden)

    Alberto J Lopez

    2015-04-01

    Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  8. Understanding autism and other neurodevelopmental disorders through experimental translational neurobehavioral models

    NARCIS (Netherlands)

    Homberg, J.R.; Kyzar, E.J.; Nguyen, M; Norton, W.H.; Pittman, J.; Poudel, M.K.; Gaikwad, S.; Nakamura, S.; Koshiba, M.; Yamanouchi, H.; Scattoni, M.L.; Ullman, J.F.; Diamond, D.M.; Kaluyeva, A.A.; Parker, M.O.; Klimenko, V.M.; Apryatin, S.A.; Brown, R.E.; Song, C.; Gainetdinov, R.R.; Gottesman, II; Kalueff, A.V.

    2016-01-01

    Neurodevelopmental disorders (NDDs) are highly prevalent and severely debilitating brain illnesses caused by aberrant brain growth and development. Resulting in cognitive, social, motor, language and affective disabilities, common NDDs include autism spectrum disorder (ASD), intellectual disability,

  9. Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years After Initial Diagnosis.

    Science.gov (United States)

    Gillberg, I Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher

    2016-01-01

    We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had never met criteria for an additional psychiatric/neurodevelopmental diagnosis and more than half had ongoing comorbidity (most commonly either ADHD or depression or both). Any psychiatric comorbidity increased the risk of poorer outcome. The minority of the AS group who no longer met criteria for a full diagnosis of an autism spectrum disorder were usually free of current psychiatric comorbidity. The high rate of psychiatric/neurodevelopmental comorbidities underscores the need for a full psychiatric/neurodevelopmental assessment at follow-up of males with AS.

  10. Rapamycin Prevents Seizures After Depletion of STRADA in a Rare Neurodevelopmental Disorder

    NARCIS (Netherlands)

    Parker, Whitney E.; Orlova, Ksenia A.; Parker, William H.; Birnbaum, Jacqueline F.; Krymskaya, Vera P.; Goncharov, Dmitry A.; Baybis, Marianna; Helfferich, Jelte; Okochi, Kei; Strauss, Kevin A.; Crino, Peter B.

    2013-01-01

    A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological

  11. Relationship between motor coordination, cognitive abilities, and academic achievement in Japanese children with neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Takuya Higashionna

    2017-12-01

    Conclusion: These findings stress that it is essential to accurately identify motor coordination impairments and the interventions that would consider motor coordination problems related to cognitive abilities and academic achievement in Japanese children with neurodevelopmental disorders.

  12. The effect of pre-existing islands on disruption mitigation in MHD simulations of DIII-D

    Science.gov (United States)

    Izzo, V. A.

    2017-05-01

    Locked-modes are the most likely cause of disruptions in ITER, so large islands are expected to be common when the ITER disruption mitigation system is deployed. MHD modeling of disruption mitigation by massive gas injection is carried out for DIII-D plasmas with stationary, pre-existing islands. Results show that the magnetic topology at the q = 2 surface can affect the parallel spreading of injected impurities, and that, in particular, the break-up of large 2/1 islands into smaller 4/2 islands chains can favorably affect mitigation metrics. The direct imposition of a 4/2 mode is found to have similar results to the case in which the 4/2 harmonic grows spontaneously.

  13. Prognosis and long-term neurodevelopmental outcome in conservatively treated twin-to-twin transfusion syndrome

    Directory of Open Access Journals (Sweden)

    Ochiai Masayuki

    2011-04-01

    Full Text Available Abstract Background Amnioreduction remains a treatment option for pregnancies with twin-to-twin transfusion syndrome (TTTS not meeting criteria for laser surgery or those in which it is not feasible. Amnioreduction is a relatively simple treatment which does not require sophisticated technical equipment. Previous reports of conservative management have indicated that major neurodevelopmental impairment occurs in 14.3-26% of survivors. The purpose of this study was to investigate long-term neurodevelopmental outcome in conservatively treated TTTS. Methods During the nine-year study period from January 1996 to December 2004, all pregnancies with TTTS who were admitted to our center were investigated. TTTS was diagnosed by using standard prenatal ultrasound criteria, and staged according to the criteria of Quintero et al. We reviewed gestational age at diagnosis, gestational age at delivery, the stage of TTTS at diagnosis, and diagnosis to delivery interval. Neonatal cranial ultrasound findings were reviewed and the neurodevelopmental outcomes were evaluated. Results Twenty-one pregnancies with TTTS were included. Thirteen pregnancies (62% were treated with serial amnioreduction. The mean gestational age at delivery was 28 weeks (22 - 34 weeks. The perinatal mortality rate was 42.9%. Twenty survivors were followed up until at least 3 years of age. The mean age at follow-up was 6.3 years (3 - 12 years. Six children (30% had neurodevelopmental impairment. Four children (20% had major neurodevelopmental impairment and two children (10% had minor neurodevelopmental impairment. Children with neurodevelopmental impairment were delivered before 29 weeks of gestation. Conclusions Our study showed a high rate of perinatal mortality and a high rate of major neurodevelopmental impairment in conservatively treated TTTS. The long-term outcomes for the survivors with TTTS were good when survivors were delivered after 29 weeks of gestation.

  14. Neurodevelopmental outcome of infants resuscitated with air or 100% oxygen: a systematic review and meta-analysis.

    Science.gov (United States)

    Saugstad, Ola Didrik; Vento, Maximo; Ramji, Siddarth; Howard, Diantha; Soll, Roger F

    2012-01-01

    The use of air for the initial resuscitation of newborn infants has been shown to reduce neonatal mortality. However, a precise estimate of the neurodevelopmental status upon follow-up of infants resuscitated in air is lacking. To perform a meta-analysis of all studies reporting resuscitation of newborn infants with air or 100% oxygen that included follow-up data. Bibliographic databases were searched. In addition, we estimated the effect of loss to follow-up on our analysis of abnormal neurodevelopmental outcome. We identified 10 studies in which newborn infants had been randomly or quasi-randomly assigned to resuscitation with air or 100% oxygen. Three of these 10 studies had available follow-up data. A total of 678 infants were enrolled at centers that performed follow-up of these infants. Of these, 113 died, leaving 565 infants potentially eligible for follow-up. A total of 414 children were evaluated (73% of eligible children; 195 resuscitated with air and 219 with 100% oxygen). In the air group, 12.8% of infants had an abnormal neurodevelopmental outcome, compared with 10.5% in the 100% oxygen group [typical relative risk (RR) 1.24, 95% confidence interval 0.73-2.10]. This is consistent with an RR of abnormal development as low as 0.41 or as high as 2.28. Long-term follow-up did not detect any significant differences in these two groups regarding abnormal development. However, the results are imprecise and could be consistent with significant harm or benefit. Copyright © 2012 S. Karger AG, Basel.

  15. Neurodevelopmental problems at 18 months among children exposed to paracetamol in utero: a propensity score matched cohort study.

    Science.gov (United States)

    Vlenterie, Richelle; Wood, Mollie E; Brandlistuen, Ragnhild Eek; Roeleveld, Nel; van Gelder, Marleen Mhj; Nordeng, Hedvig

    2016-12-01

    Previous studies showed that children exposed to paracetamol during fetal life might have an increased risk of neurodevelopmental problems. Since paracetamol is one of the most commonly used medications during pregnancy, even small increases in the risk of neurodevelopmental problems may have considerable implications for public health. Using data from the Norwegian Mother and Child Cohort Study, we applied propensity score (PS) matching to examine associations between prenatal paracetamol exposure and neurodevelopmental problems among children at 18 months of age. Paracetamol use was classified into short-term (< 28 days) and long-term (≥ 28 days) of exposure. Of the 51 200 pregnancies included in our study, 40.5% of mothers ( n  = 20 749) used paracetamol at least once during pregnancy. In the PS-matched analyses, long-term paracetamol exposure during pregnancy was associated with communication problems [odds ratio (OR): 1.38, 95% confidence interval (CI) 0.98-1.95) and delayed motor milestone attainment (OR: 1.35, 95% CI 1.07-1.70). We did not observe increased risks after short-term exposure. Sensitivity analyses for several indications showed similar effects as the PS-matched analyses, suggesting no confounding by indication. Long-term exposure to paracetamol in utero was associated with modestly increased risks of motor milestone delay and impaired communication skills among children at 18 months. Caution is warranted when considering long-term use of paracetamol during pregnancy; however, women with severe pain conditions should not be deprived of appropriate pharmacotherapy.

  16. Abstract on the Effective validation of both new and existing methods for the observation and forecasting of volcanic emissions

    Science.gov (United States)

    Sathnur, Ashwini

    2017-04-01

    Validation of the Existing products of the Remote Sensing instruments Review Comment Number 1 Ground - based instruments and space - based instruments are available for remote sensing of the Volcanic eruptions. Review Comment Number 2 The sunlight spectrum appears over the volcanic geographic area. This sunlight is reflected with the image of the volcano geographic area, to the satellite. The satellite captures this emitted spectrum of the image and further calculates the occurrences of the volcanic eruption. Review Comment Number 3 This computation system derives the presence and detection of sulphur dioxide and Volcanic Ash in the emitted spectrum. The temperature of the volcanic region is also measured. If these inputs derive the possibility of occurrence of an eruption, then the data is manually captured by the system for further usage and hazard mitigation. Review Comment Number 4 The instrument is particularly important in capturing the volcanogenic signal. This capturing operation should be carried out during the appropriate time of the day. This is carried out ideally at the time of the day when the reflected image spectra is best available. Capturing the data is not advisable to be performed at the night time, as the sunlight spectra is at its minimum. This would lead to erroneous data interpretation, as there is no sunlight for reflection of the volcanic region. Thus leading to the least capture of the emitted light spectra. Review Comment Number 5 An ideal area coverage of the spectrometer is mandatory. This is basically for the purpose of capturing the right area of data, in order to precisely derive the occurrence of a volcanic eruption. The larger the spatial resolution, there would be a higher capture of the geographic region, and this would lead to a lesser precise data capture. This would lead to missing details in the data capture. Review Comment Number 6 Ideal qualities for the remote sensing instrument are mentioned below:- Minimum "false

  17. The Neurodevelopmental Basis of Early Childhood Disruptive Behavior: Irritable and Callous Phenotypes as Exemplars.

    Science.gov (United States)

    Wakschlag, Lauren S; Perlman, Susan B; Blair, R James; Leibenluft, Ellen; Briggs-Gowan, Margaret J; Pine, Daniel S

    2017-11-17

    The arrival of the Journal's 175th anniversary occurs at a time of recent advances in research, providing an ideal opportunity to present a neurodevelopmental roadmap for understanding, preventing, and treating psychiatric disorders. Such a roadmap is particularly relevant for early-childhood-onset neurodevelopmental conditions, which emerge when experience-dependent neuroplasticity is at its peak. Employing a novel developmental specification approach, this review places recent neurodevelopmental research on early childhood disruptive behavior within the historical context of the Journal. The authors highlight irritability and callous behavior as two core exemplars of early disruptive behavior. Both phenotypes can be reliably differentiated from normative variation as early as the first years of life. Both link to discrete pathophysiology: irritability with disruptions in prefrontal regulation of emotion, and callous behavior with abnormal fear processing. Each phenotype also possesses clinical and predictive utility. Based on a nomologic net of evidence, the authors conclude that early disruptive behavior is neurodevelopmental in nature and should be reclassified as an early-childhood-onset neurodevelopmental condition in DSM-5. Rapid translation from neurodevelopmental discovery to clinical application has transformative potential for psychiatric approaches of the millennium.

  18. Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders

    Science.gov (United States)

    Schubert, D; Martens, G J M; Kolk, S M

    2015-01-01

    The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies. PMID:25450230

  19. Effect of co-existing kaolinite and goethite on the aggregation of graphene oxide in the aquatic environment.

    Science.gov (United States)

    Huang, Guanxing; Guo, Huiyuan; Zhao, Jian; Liu, Yonghong; Xing, Baoshan

    2016-10-01

    Broad applications of graphene oxide (GO) will result in the release of GO into aquatic environments, where clay minerals and metal (hydr)oxides are commonly present. Thereby the interactions between GO and a binary system containing clay minerals and metal (hydr)oxides can occur. We investigated the aggregation of GO with kaolinite and kaolinite-goethite associations (KGAs) in aquatic systems under different pHs, ionic strengths, and GO concentrations. GO suspension was unstable at low pHs, and the aggregation of GO occurred in the presence of KGA-4% and KGA-10% until pH 5 and 6, respectively. Kaolinite decreased the critical coagulation concentration (CCC) of GO at pH 5.5 from around 50 to 20 mM NaCl due to the reduced energy barrier. Heteroaggregation of GO with KGAs was extremely sensitive to ionic strength at pH 5.5, and the CCC of GO in the presence of KGA-10% increased from less than 1 mM NaCl to 5 mM NaCl with the increase of pH from 5.5 to 9. The heteroaggregation extent of GO with KGAs was enhanced firstly, then reduced with the increase of GO concentrations at pH 5.0, which is likely because KGA plates were more efficiently wrapped by large-size GO sheets with increasing GO concentrations. These findings are useful for understanding and predicting the fate of GO in the relatively complicated aquatic and soil environments where binary minerals co-exist. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Teaching-skills training programs for family medicine residents: systematic review of formats, content, and effects of existing programs.

    Science.gov (United States)

    Lacasse, Miriam; Ratnapalan, Savithiri

    2009-09-01

    To review the literature on teaching-skills training programs for family medicine residents and to identify formats and content of these programs and their effects. Ovid MEDLINE (1950 to mid-July 2008) and the Education Resources Information Center database (pre-1966 to mid-July 2008) were searched using and combining the MeSH terms teaching, internship and residency, and family practice; and teaching, graduate medical education, and family practice. The initial MEDLINE and Education Resources Information Center database searches identified 362 and 33 references, respectively. Titles and abstracts were reviewed and studies were included if they described the format or content of a teaching-skills program or if they were primary studies of the effects of a teaching-skills program for family medicine residents or family medicine and other specialty trainees. The bibliographies of those articles were reviewed for unidentified studies. A total of 8 articles were identified for systematic review. Selection was limited to articles published in English. Teaching-skills training programs for family medicine residents vary from half-day curricula to a few months of training. Their content includes leadership skills, effective clinical teaching skills, technical teaching skills, as well as feedback and evaluation skills. Evaluations mainly assessed the programs' effects on teaching behaviour, which was generally found to improve following participation in the programs. Evaluations of learner reactions and learning outcomes also suggested that the programs have positive effects. Family medicine residency training programs differ from all other residency training programs in their shorter duration, usually 2 years, and the broader scope of learning within those 2 years. Few studies on teaching-skills training, however, were designed specifically for family medicine residents. Further studies assessing the effects of teaching-skills training in family medicine residents are

  1. Extensions of Existing Methods for Use with a New Class of Experimental Designs Useful when There Is Treatment Effect Contamination

    Science.gov (United States)

    Rhoads, Christopher

    2011-01-01

    Researchers planning a randomized field trial to evaluate the effectiveness of an educational intervention often face the following dilemma. They plan to recruit schools to participate in their study. The question is, "Should the researchers randomly assign individuals (either students or teachers, depending on the intervention) within schools to…

  2. On the existence of a negative pasteur effect in yeasts classified in the genus Brettanomyces Kufferath et van Laer

    NARCIS (Netherlands)

    Scheffers, W.A.; Wikén, T.; Verhaar, A.J.M.

    1961-01-01

    Even at a mere glance at the extensive literature on the influence of elementary molecular oxygen on the alcoholic fermentation in living yeast cells and various yeast preparations it is evident that so far most works have been concerned with the inhibiting effect produced by this gas on the rate

  3. Does Big-Fish-Little-Pond Effect Always Exist? Investigation of Goal Orientations as Moderators in the Hong Kong Context

    Science.gov (United States)

    Cheng, Rebecca Wing-yi; McInerney, Dennis M.; Mok, Magdalena Mo Ching

    2014-01-01

    The big-fish-little-pond effect (BFLPE) posits that students with the same ability will have higher academic self-concepts when they are in low-ability classes than in high-ability classes. Our research puts the BFLPE under scrutiny by examining goal orientations as the moderators that may affect the size of the BFLPE. We collected data on…

  4. The effectiveness of business codes: a critical examination of existing studies and the development of an integrated research model

    NARCIS (Netherlands)

    S.P. Kaptein (Muel); M.S. Schwartz (Mark)

    2008-01-01

    textabstractBusiness codes are a widely used management instrument. Research into the effectiveness of business codes has, however, produced conflicting results. The main reasons for the divergent findings are: varying definitions of key terms; deficiencies in the empirical data and methodologies

  5. Influenza vaccination in children with neurologic or neurodevelopmental disorders.

    Science.gov (United States)

    Smith, Michael; Peacock, Georgina; Uyeki, Timothy M; Moore, Cynthia

    2015-05-11

    Children with neurologic or neurodevelopmental disorders (NNDDs) are at increased risk of complications from influenza. Although the Advisory Committee on Immunization Practices (ACIP) has recognized NNDDs as high-risk conditions for influenza complications since 2005, little is known about influenza vaccination practices in this population. CDC collaborated with Family Voices, a national advocacy group for children with special healthcare needs, to recruit parents of children with chronic medical conditions. Parents were surveyed about their knowledge, attitudes, and practices surrounding influenza vaccination. The primary outcome of interest was parental report of vaccination, or intent to vaccinate, at the time of survey participation. CDC also collaborated with the American Academy of Pediatrics to recruit primary care and specialty physicians who provide care for high-risk children, specifically those with neurologic conditions. The primary outcome was physician recognition of ACIP high-risk influenza conditions. 2138 surveys were completed by parents of children with high-risk conditions, including 1143 with at least one NNDD. Overall, 50% of children with an NNDD were vaccinated, or their parents planned to have them vaccinated against influenza. Among all 2138 children, in multivariable analysis, the presence of a respiratory condition and prior seasonal influenza vaccination was significantly associated with receipt or planned current season influenza vaccination, but the presence of an NNDD was not. 412 pediatricians completed the provider survey. Cerebral palsy was recognized as a high-risk influenza condition by 74% of physician respondents, but epilepsy (51%) and intellectual disability (46%) were less commonly identified. Our estimates of influenza vaccination in children with NNDDs are comparable to published reports of vaccination in healthy children, which continue to be suboptimal. Education of parents of children with NNDDs and healthcare

  6. Neurodevelopmental origins of bipolar disorder: iPSC models.

    Science.gov (United States)

    O'Shea, K Sue; McInnis, Melvin G

    2016-06-01

    Bipolar disorder (BP) is a chronic neuropsychiatric condition characterized by pathological fluctuations in mood from mania to depression. Adoption, twin and family studies have consistently identified a significant hereditary component to BP, yet there is no clear genetic event or consistent neuropathology. BP has been suggested to have a developmental origin, although this hypothesis has been difficult to test since there are no viable neurons or glial cells to analyze, and research has relied largely on postmortem brain, behavioral and imaging studies, or has examined proxy tissues including saliva, olfactory epithelium and blood cells. Neurodevelopmental factors, particularly pathways related to nervous system development, cell migration, extracellular matrix, H3K4 methylation, and calcium signaling have been identified in large gene expression and GWAS studies as altered in BP. Recent advances in stem cell biology, particularly the ability to reprogram adult somatic tissues to a pluripotent state, now make it possible to interrogate these pathways in viable cell models. A number of induced pluripotent stem cell (iPSC) lines from BP patient and healthy control (C) individuals have been derived in several laboratories, and their ability to form cortical neurons examined. Early studies suggest differences in activity, calcium signaling, blocks to neuronal differentiation, and changes in neuronal, and possibly glial, lineage specification. Initial observations suggest that differentiation of BP patient-derived neurons to dorsal telencephalic derivatives may be impaired, possibly due to alterations in WNT, Hedgehog or Nodal pathway signaling. These investigations strongly support a developmental contribution to BP and identify novel pathways, mechanisms and opportunities for improved treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Social neuroscience, empathy, brain integration, and neurodevelopmental disorders.

    Science.gov (United States)

    Harris, James C

    2003-08-01

    Paul MacLean has investigated integrated brain functioning through selected brain lesions in animals that disturb circuits necessary for complex behaviors, such as social displays. MacLean is unique in his comparative neurobehavioral approach that emphasizes the evolutionary origins of parenting and social behaviors and the implications of brain changes in the evolution from reptiles (social displays) to mammals (nursing, audiovocal communication, play) to man (self-awareness, intentionality, social context) that link affect and cognition. Subjectively, how "looking with feeling toward others," the basic element in empathy, evolved has been a central concern of his. Neuroimaging studies of social cognition, mother-infant communication, moral behavior, forgiveness, and trust are consistent with particular brain systems being activated in cooperative social behaviors. The identification of mirror neurons is pertinent to MacLean's model of isopraxis and studies of thalamocortical resonances may be pertinent to his neurobehavioral models. Studies of behavioral phenotypes in human neurodevelopmental disorders are consistent with MacLean's model of brain circuits being linked to complex behaviors during development. In autistic disorder, the behavioral phenotype involves disrupted social communication, deviant imaginative play, and motor stereotypies. In Lesch-Nyhan syndrome (LNS), self-injury occurs in individuals with normal sensory systems intact who require and request physical restraint to prevent self-injury; they ask for assistance from others to prevent them from harming themselves. Autism involves the lack of subjective awareness of others intentions and LNS involves a failure in self-regulation and self-control of self-injurious behavior. MacLean's models laid the groundwork for studies focused on understanding brain functioning in these conditions.

  8. Pediatric neuroenhancement: ethical, legal, social, and neurodevelopmental implications.

    Science.gov (United States)

    Graf, William D; Nagel, Saskia K; Epstein, Leon G; Miller, Geoffrey; Nass, Ruth; Larriviere, Dan

    2013-03-26

    The use of prescription medication to augment cognitive or affective function in healthy persons-or neuroenhancement-is increasing in adult and pediatric populations. In children and adolescents, neuroenhancement appears to be increasing in parallel to the rising rates of attention-deficit disorder diagnoses and stimulant medication prescriptions, and the opportunities for medication diversion. Pediatric neuroenhancement remains a particularly unsettled and value-laden practice, often without appropriate goals or justification. Pediatric neuroenhancement presents its own ethical, social, legal, and developmental issues, including the fiduciary responsibility of physicians caring for children, the special integrity of the doctor-child-parent relationship, the vulnerability of children to various forms of coercion, distributive justice in school settings, and the moral obligation of physicians to prevent misuse of medication. Neurodevelopmental issues include the importance of evolving personal authenticity during childhood and adolescence, the emergence of individual decision-making capacities, and the process of developing autonomy. This Ethics, Law, and Humanities Committee position paper, endorsed by the American Academy of Neurology, Child Neurology Society, and American Neurological Association, focuses on various implications of pediatric neuroenhancement and outlines discussion points in responding to neuroenhancement requests from parents or adolescents. Based on currently available data and the balance of ethics issues reviewed in this position paper, neuroenhancement in legally and developmentally nonautonomous children and adolescents without a diagnosis of a neurologic disorder is not justifiable. In nearly autonomous adolescents, the fiduciary obligation of the physician may be weaker, but the prescription of neuroenhancements is inadvisable because of numerous social, developmental, and professional integrity issues.

  9. Impact of clinical exomes in neurodevelopmental and neurometabolic disorders.

    Science.gov (United States)

    Evers, Christina; Staufner, Christian; Granzow, Martin; Paramasivam, Nagarajan; Hinderhofer, Katrin; Kaufmann, Lilian; Fischer, Christine; Thiel, Christian; Opladen, Thomas; Kotzaeridou, Urania; Wiemann, Stefan; Schlesner, Matthias; Eils, Roland; Kölker, Stefan; Bartram, Claus R; Hoffmann, Georg F; Moog, Ute

    2017-08-01

    Whole exome sequencing (WES) is well established in research and is now being introduced into clinically indicated diagnostics (so-called clinical exomes). We evaluated the diagnostic yield and clinical implications of WES in 72 patients from 60 families with undiagnosed neurodevelopmental disorders (NDD), neurometabolic disorders, and dystonias. Pathogenic or likely pathogenic variants leading to a molecular diagnosis could be identified in 21 of the 60 families (overall 35%, in 36% of patients with NDD, in 43% of patients with neurometabolic disorders, in 25% of patients with dystonias). In one family two coexisting autosomal recessive diseases caused by homozygous pathogenic variants in two different genes were diagnosed. In another family, a homozygous frameshift variant in STRADA was found to cause a severe NDD with early onset epilepsy, brain anomalies, hypotonia, heart defect, nephrocalcinosis, macrocephaly and distinctive facies so far designated as PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. In 7 of the 21 families with a molecular diagnosis the pathogenic variants were only identified by clinical follow-up, manual reevaluation of the literature, a change of filter setting, and/or reconsideration of inheritance pattern. Most importantly, clinical implications included management changes in 8 cases and impact on family planning in 20 families with a molecular diagnosis. This study shows that reevaluation and follow-up can improve the diagnostic rate and that WES results have important implications on medical management and family planning. Furthermore, we could confirm STRADA as a gene associated with syndromic ID but find it questionable if the current designation as PMSE depicts the most important clinical features. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Mediating effect of decline in social activities on urinary incontinence and negative mood: Do sex and marital differences exist?

    Science.gov (United States)

    Bai, Xue; Leung, Doris Yin Ping; Lai, Claudia Kam Yuk; Chong, Alice Ming Lin; Chi, Iris

    2017-11-01

    We tested the mediating effect of decline in social participation on urinary incontinence (UI) and negative mood in older adults by sex and marital status. We carried out secondary analysis of data collected from 5301 Chinese adults aged 60 years or older in Hong Kong who had completed an initial screening instrument for subsidized long-term care services in 2010. Path analysis within structural equation modeling was carried out. Satisfactory model fit was obtained: male-married group (n = 1949, standardized root means squared residual [SRMR] = 0.034, robust root mean square error of approximation [R-RMSEA] = 0.045, robust comparative fit index [R-CFI] = 0.965), male-other group (n = 519, SRMR = 0.023, R-RMSEA = 0.011, R-CFI = 0.988), female-married group (n = 948, SRMR = 0.018, R-RMSEA = 0.002, R-CFI = 1.000) and female-other group (n = 2251, SRMR = 0.023, R-RMSEA = 0.048, R-CFI = 0.970). In the male-married subsample, UI had both a significant direct effect (β = 0.046) and significant indirect effect on mood through decline in social participation (β = 0.021); for the female-other subsample, UI (β = 0.058) and decline in social participation (β = 0.335) had significant direct effects on negative mood. Decline in social participation had a significant direct effect on negative mood in the male-other subsample (β = 0.306) and the female-married subsample (β = 0.325). Decline in social participation mediated the relationship between UI and negative mood in married older men, but not male-other group or women. It is important to recognize these sex and marital status differences, and expand social participation opportunities for UI patients. Geriatr Gerontol Int 2017; 17: 1829-1836. © 2017 Japan Geriatrics Society.

  11. Functional argument for the existence of an avian nitric oxide synthase in muscle mitochondria: effect of cold acclimation.

    Science.gov (United States)

    Rey, Benjamin; Roussel, Damien; Teulier, Loïc; Eyenga, Pierre; Degletagne, Cyril; Belouze, Maud; Duchamp, Claude

    2011-01-03

    We report the first evidence of a mitochondrial NO synthase (mtNOS) in bird skeletal muscle. In vitro, mtNOS activity stimulated by L-arginine reduced intermyofibrillar mitochondrial oxygen uptake and ATP synthesis rates, stimulated endogenous H(2)O(2) generation, but had no effect on oxidative phosphorylation efficiency. Arginine-induced effects were fully reversed by L-NAME, a known NOS inhibitor. When ducklings were cold exposed for 4 weeks, muscle mitochondria displayed an increased state 3 respiration, a reduced H(2)O(2) generation but no significant alteration in mtNOS activity. We conclude that mtNOS is expressed in avian skeletal muscle. Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. Requirements for existing buildings

    DEFF Research Database (Denmark)

    Thomsen, Kirsten Engelund; Wittchen, Kim Bjarne

    This report collects energy performance requirements for existing buildings in European member states by June 2012.......This report collects energy performance requirements for existing buildings in European member states by June 2012....

  13. The effect of pre-existing affect on the sexual responses of women with and without a history of childhood sexual abuse.

    Science.gov (United States)

    Rellini, Alessandra H; Elinson, Samantha; Janssen, Erick; Meston, Cindy M

    2012-04-01

    Women with a history of childhood sexual abuse (CSA) are at greater risk for experiencing sexual problems in their adult lives. Yet, little is known about the possible role of cognitive and affective mechanisms in the development of sexual arousal difficulties in this population. This study investigated the role of pre-existing affect (affect prior to exposure to sexual stimuli) on genital responses, subjective sexual arousal, and affect elicited during the presentation of erotic film excerpts in a community sample of 25 women with and 25 women without a history of CSA. The CSA group showed greater pre-existing negative affect and smaller genital responses to the erotic film stimuli compared to the NSA group. Findings support a moderating effect of CSA, in that pre-existing negative affect was associated with strength of genital responses in the NSA but not in the CSA group. The results did not support a mediation model of pre-existing negative affect as an explanation for smaller physiological sexual responses in the CSA group. Taken together, the findings suggest that pre-existing affect may be more relevant for women with no history of CSA and call for more research on factors implicated in impaired sexual responses in women with a history of CSA.

  14. Child functional characteristics explain child and family outcomes better than diagnosis: Population-based study of children with autism or other neurodevelopmental disorders/disabilities.

    Science.gov (United States)

    Miller, Anton; Shen, Jane; Mâsse, Louise C

    2016-06-15

    Allocation of resources for services and supports for children with neurodevelopmental disorders/disabilities (NDD/D) is often based on the presence of specific health conditions. This study investigated the relative roles of a child's diagnosed health condition and neurodevelopmental and related functional characteristics in explaining child and family health and well-being. The data on children with NDD/D (ages 5 to 14; weighted n = 120,700) are from the 2006 Participation and Activity Limitation Survey (PALS), a population-based Canadian survey of parents of children with functional limitations/disabilities. Direct and indirect effects of child diagnosis status-autism spectrum disorder (ASD)/not ASD-and functional characteristics (particularly, ASD-related impairments in speech, cognition, and emotion and behaviour) on child participation and family health and well-being were investigated in a series of structural equation models, while controlling for covariates. All models adequately fitted the data. Child ASD diagnosis was significantly associated with child participation and family health and well-being. When ASD-related child functional characteristics were added to the model, all direct effects from child diagnosis on child and family outcomes disappeared; the effect of child diagnosis on child and family outcomes was fully mediated via ASD-related child functional characteristics. Children's neurodevelopmental functional characteristics are integral to understanding the child and family health-related impact of neurodevelopmental disorders such as ASD. These findings have implications for the relative weighting given to functional versus diagnosis-specific factors in considering needs for services and supports.

  15. The greenhouse effect does not exist. Het broeikaseffect bestaat niet; De mythe van de ondergang van het milieu

    Energy Technology Data Exchange (ETDEWEB)

    Beckman, K.

    1992-01-01

    The average Dutch citizen considers the environmental problems as serious. It is believed that the pessimistic scenarios and forecasts are based on scientific facts. The author does not agree. The apocalyptic scenarios start from a number of concrete threats: the greenhouse effect, the ozone layer depletion, the acidification, the increasing water and air pollution, the growing amount of toxic materials in the environment, the exhaustion of base materials, deforestation, overpopulation, and the extinction of species of animals and plants. If every threat is considered by itself, than it appears that most of these threats are based on misunderstandings, half truths, ill-founded speculations and sometimes even a lie. According to the author environmental problems can be identified, but in most cases they are not disastrous. There is no environmental crises. The author suggests that politicians draw benefit from the increased attention for the environment. Keeping up the idea of an environmental crisis helps the politicians to justify a tax raise. Or it helps the society criticaster to criticize the consumer society. Other motives to think that the environment is going to be destroyed are fears for fast technological developments, concern about the individualism and increasing anonymity in the urbanized Netherlands, outrage over hunger and other misery in the world. Real problems, but no link with the environmental problems. 41 refs.

  16. Self-assembled polymeric vectors mixtures: characterization of the polymorphism and existence of synergistic effects in photodynamic therapy

    Science.gov (United States)

    Till, Ugo; Gibot, Laure; Mingotaud, Christophe; Vicendo, Patricia; Rols, Marie-Pierre; Gaucher, Mireille; Violleau, Frédéric; Mingotaud, Anne-Françoise

    2016-08-01

    The objective of this work was to assess the relation between the purity of polymeric self-assemblies vectors solution and their photodynamic therapeutic efficiency. For this, several amphiphilic block copolymers of poly(ethyleneoxide-b-ε-caprolactone) have been used to form self-assemblies with different morphologies (micelles, worm-like micelles or vesicles). In a first step, controlled mixtures of preformed micelles and vesicles have been characterized both by dynamic light scattering and asymmetrical flow field flow fractionation (AsFlFFF). For this, a custom-made program, STORMS, was developed to analyze DLS data in a thorough manner by providing a large set of fitting parameters. This showed that DLS only sensed the larger vesicles when the micelles/vesicles ratio was 80/20 w/w. On the other hand, AsFlFFF allowed clear detection of the presence of micelles when this same ratio was as low as 10/90. Subsequently, the photodynamic therapy efficiency of various controlled mixtures was assessed using multicellular spheroids when a photosensitizer, pheophorbide a, was encapsulated in the polymer self-assemblies. Some mixtures were shown to be as efficient as monomorphous systems. In some cases, mixtures were found to exhibit a higher PDT efficiency compared to the individual nano-objects, revealing a synergistic effect for the efficient delivery of the photosensitizer. Polymorphous vectors can therefore be superior in therapeutic applications.

  17. A preclinical animal model to assess the effect of pre-existing immunity on AAV-mediated gene transfer.

    Science.gov (United States)

    Li, Hua; Lin, Shih-Wen; Giles-Davis, Wynetta; Li, Yan; Zhou, Dongming; Xiang, Zhi Quan; High, Katherine A; Ertl, Hildegund C J

    2009-07-01

    Hepatic adeno-associated virus (AAV)-serotype 2-mediated gene transfer results in sustained transgene expression in experimental animals but not in human subjects. We hypothesized that loss of transgene expression in humans might be caused by immune memory mechanisms that become reactivated upon AAV vector transfer. Here, we tested the effect of immunological memory to AAV capsid on AAV-mediated gene transfer in a mouse model. Upon hepatic transfer of an AAV2 vector expressing human factor IX (hF.IX), mice immunized with adenovirus (Ad) vectors expressing AAV8 capsid before AAV2 transfer developed less circulating hF.IX and showed a gradual loss of hF.IX gene copies in liver cells as compared to control animals. This was not observed in mice immunized with an Ad vectors expressing AAV2 capsid before transfer of rAAV8-hF.IX vectors. The lower hF.IX expression was primarily linked to AAV-binding antibodies that lacked AAV-neutralizing activity in vitro rather than to AAV capsid-specific CD8(+) T cells.

  18. State-level infrastructure and economic effects of switchgrass cofiring with coal in existing power plants for carbon mitigation.

    Science.gov (United States)

    Morrow, William R; Griffin, W Michael; Matthews, H Scott

    2007-10-01

    This paper presents a linear programming (LP) methodology for estimating the cost of reducing a state's coal-fired power plant carbon dioxide emissions by cofiring switchgrass and coal. LP modeling allows interplay between regionally specific switchgrass production forecasts, coal plant locations, and individual coal plant historic performance data to determine an allocation of switchgrass minimizing cost or maximizing carbon reduction. The LP methodology is applied to two states, Pennsylvania (PA) and Iowa (IA), and results are presented with a discussion of modeling assumptions, techniques, and carbon mitigation policy implications. The LP methodology estimates that, in PA, 4.9 million tons of CO2/year could be mitigated at an average cost of less than $34/ton of CO2 and that, in IA, 7 million tons of CO2/year could be mitigated at an average Cost of Mitigation of $27/ton of CO2. Because the factors determining the cofiring costs vary so much between the two states, results suggest that cofiring costs will also vary considerably between different U.S. regions. A national level analysis could suggest a lowest-cost cofiring region. This paper presents techniques and assumptions that can simplify biomass energy policy analysis with little effect on analysis conclusions.

  19. Tribal Proclivity and its Effects on the Cooperate Existence of Nigeria in the Centenary Era: An Islamic Perspective

    Directory of Open Access Journals (Sweden)

    USMAN JIMOH MUHAMMAD

    2015-12-01

    Full Text Available The paper consists of seven sub-sections namely, the introduction, a flash on the prevalence of tribal proclivity in Nigeria, causes of tribal proclivity among Nigerians and its effects. Other aspect of the paper includes the Islamic perspective on tribal proclivity in Nigeria, recommendations and conclusion. The introduction briefly appraises the historical composition of Nigeria in the early nineteen century and its amalgamation in the year 1914. Reference is being made in the paper to cases of tribal proclivity in Nigeria while the causes of tribal penchant include unemployment, selfishness of some politicians, lack of patience and endurance by citizens in their relationship among themselves. Tribal proclivity the paper affirms results into insecurity of lives and properties, portrays evidence of lack of unity and bad governance. The paper examines some relevant verses and prophetic traditions in a bid to redress the situation and recommends that the government and the well to problem of unemployment in the nation. In addition, religious do people in the society should join hands together towards addressing the scholars and other orientation bodies must reorient people towards peaceful coexistence among themselves.

  20. Neurodevelopmental outcome of extremely low-birth-weight infants randomly assigned to restrictive or liberal hemoglobin thresholds for blood transfusion.

    Science.gov (United States)

    Whyte, Robin K

    2012-08-01

    Surviving extremely low-birth-weight infants are at risk of severe neurodevelopmental disability. Transfusion with packed red cells is almost universal in the care of these infants, but the hemoglobin threshold at which these transfusions should be given is unclear. Different clinical trials of restrictive (low hemoglobin) versus liberal (high hemoglobin) thresholds have addressed either neurodevelopmental outcomes at 18-21 months of corrected gestational age or psychological tests and brain imaging at 8-15 years of age. Early follow-up shows differences in cognitive outcome favoring the liberal strategy, but as a post hoc secondary outcome. The childhood studies favor the restrictive strategy, but include major methodological problems of secondary recruitment. No firm conclusion can be reached, other than to report that serious adverse effects may be attributable to one or other of these strategies, that prudent practice is to remain within trial protocols, and that further redesigned clinical trials are required. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

    Science.gov (United States)

    Andersen, Stine Linding; Carlé, Allan; Karmisholt, Jesper; Pedersen, Inge Bülow; Andersen, Stig

    2017-07-01

    Fetal programming is a long-standing, but still evolving, concept that links exposures during pregnancy to the later development of disease in the offspring. A fetal programming effect has been considered within different endocrine axes and in relation to different maternal endocrine diseases. In this critical review, we describe and discuss the hypothesis of fetal programming by maternal thyroid dysfunction in the context of fetal brain development and neurodevelopmental disorders in the offspring. Thyroid hormones are important regulators of early brain development, and evidence from experimental and observational human studies have demonstrated structural and functional abnormalities in the brain caused by the lack or excess of thyroid hormone during fetal brain development. The hypothesis that such abnormalities introduced during early fetal brain development increase susceptibility for the later onset of neurodevelopmental disorders in the offspring is biologically plausible. However, epidemiological studies on the association between maternal thyroid dysfunction and long-term child outcomes are observational in design, and are challenged by important methodological aspects. © 2017 European Society of Endocrinology.

  2. Neurodevelopmental disorders in children born to mothers with systemic lupus erythematosus.

    Science.gov (United States)

    Vinet, É; Pineau, C A; Clarke, A E; Fombonne, É; Platt, R W; Bernatsky, S

    2014-10-01

    Children born to women with systemic lupus erythematosus seem to have a potentially increased risk of neurodevelopmental disorders compared to children born to healthy women. Recent experimental data suggest in utero exposure to maternal antibodies and cytokines as important risk factors for neurodevelopmental disorders. Interestingly, women with systemic lupus erythematosus display high levels of autoantibodies and cytokines, which have been shown, in animal models, to alter fetal brain development and induce behavioral anomalies in offspring. Furthermore, subjects with systemic lupus erythematosus and neurodevelopmental disorders share a common genetic predisposition, which could impair the fetal immune response to in utero immunologic insults. Moreover, systemic lupus erythematosus pregnancies are at increased risk of adverse obstetrical outcomes and medication exposures, which have been implicated as potential risk factors for neurodevelopmental disorders. In this article, we review the current state of knowledge on neurodevelopmental disorders and their potential determinants in systemic lupus erythematosus offspring. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  3. The Effects of Pre-Existing Hyponatremia and Subsequent-Developing Acute Kidney Injury on In-Hospital Mortality: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Sung Woo Lee

    Full Text Available Both hyponatremia and acute kidney injury (AKI are common and harmful in hospitalized patients. However, their combined effects on patient mortality have been little studied.We retrospectively enrolled 19191 adult patients who were admitted for 1 year. Pre-existing hyponatremia was defined as a serum sodium level < 135 mmol/L on the first measurement of their admission. AKI was defined as a rise in serum creatinine by ≥ 26.5 μmol/L or ≥ 1.5 times of the baseline value of creatinine during the hospital stay.The prevalence of pre-existing hyponatremia was 8.2%. During a median 6.0 days of hospital stay, the incidence rates of AKI and in-hospital patient mortality were 5.1% and 0.9%, respectively. Pre-existing hyponatremia independently predicted AKI development and in-hospital mortality (adjusted hazard ratio [HR] 1.300, P = 0.004; HR 2.481, P = 0.002, respectively. Pre-existing hyponatremia and subsequent development of AKI increased in-hospital mortality by 85 times, compared to the patients with normonatremia and no AKI. In subgroup analysis, the AKI group showed higher rates of de novo hypernatremia than the non-AKI group during the admission. De novo hypernatremia, which might be associated with over-correction of hyponatremia, increased in-hospital mortality (HR 3.297, P <0.001, and patients with AKI showed significantly higher rates of de novo hypernatremia than patients without AKI (16.2% vs. 1.4%, P < 0.001, respectively.Pre-existing hyponatremia may be associated with the development of AKI in hospitalized patients, and both hyponatremia and hospital-acquired AKI could have a detrimental effect on short term patient mortality, which might be related to the inappropriate correction of hyponatremia in AKI patients.

  4. Prenatal and postnatal animal models of immune activation: relevance to a range of neurodevelopmental disorders.

    Science.gov (United States)

    Harvey, Louise; Boksa, Patricia

    2012-10-01

    Epidemiological evidence has established links between immune activation during the prenatal or early postnatal period and increased risk of developing a range of neurodevelopment disorders in later life. Animal models have been used to great effect to explore the ramifications of immune activation during gestation and neonatal life. A range of behavioral, neurochemical, molecular, and structural outcome measures associated with schizophrenia, autism, cerebral palsy, and epilepsy have been assessed in models of prenatal and postnatal immune activation. However, the epidemiology-driven disease-first approach taken by some studies can be limiting and, despite the wealth of data, there is a lack of consensus in the literature as to the specific dose, timing, and nature of the immunogen that results in replicable and reproducible changes related to a single disease phenotype. In this review, we highlight a number of similarities and differences in models of prenatal and postnatal immune activation currently being used to investigate the origins of schizophrenia, autism, cerebral palsy, epilepsy, and Parkinson's disease. However, we describe a lack of synthesis not only between but also within disease-specific models. Our inability to compare the equivalency dose of immunogen used is identified as a significant yet easily remedied problem. We ask whether early life exposure to infection should be described as a disease-specific or general vulnerability factor for neurodevelopmental disorders and discuss the implications that either classification has on the design, strengths and limitations of future experiments. Copyright © 2012 Wiley Periodicals, Inc.

  5. Efficacy of Intensive Neurodevelopmental Treatment for Children With Developmental Delay, With or Without Cerebral Palsy.

    Science.gov (United States)

    Lee, Kyoung Hwan; Park, Jin Woo; Lee, Ho Jun; Nam, Ki Yeun; Park, Tae June; Kim, Hee Jae; Kwon, Bum Sun

    2017-02-01

    To evaluate the effectiveness of intensive neurodevelopmental treatment (NDT) on gross motor function for the children having developmental delay (DD), with or without cerebral palsy (CP). Forty-two children had intensive NDT three times weekly, 60 minutes a day, for 3 months, immediately followed by conventional NDT once or twice a week, 30 minutes a day, for another 3 months. We assessed Gross Motor Function Measure (GMFM) over three time points: before conventional NDT, before and after intensive NDT, and after 3 months of additional conventional NDT. The GMFM score in DD children significantly improved after intensive NDT, and the improvement maintained after 3 months of conventional NDT (pintensive NDT (ptreatment efficacy between the two groups. When we calculate the absence rate for comparing the compliance between intensive and conventional NDT, the absence rate was lower during the intensive NDT. Intensive NDT showed significantly improved gross motor function and higher compliance than conventional NDT. Additionally, all improvements were maintained through subsequent short-term conventional NDT. Thus, we recommend the intensive NDT program by day-hospital centers for children with DD, irrespective of accompanying CP.

  6. Influence of intrauterine and extrauterine growth on neurodevelopmental outcome of monozygotic twins

    Directory of Open Access Journals (Sweden)

    R.K. Reolon

    2008-08-01

    Full Text Available There have been indications that intrauterine and early extrauterine growth can influence childhood mental and motor function. The objective of the present study was to evaluate the influence of intrauterine growth restriction and early extrauterine head growth on the neurodevelopmental outcome of monozygotic twins. Thirty-six monozygous twin pairs were evaluated at the corrected age of 12 to 42 months. Intrauterine growth restriction was quantified using the fetal growth ratio. The effects of birth weight ratio, head circumference at birth and current head circumference on mental and motor outcomes were estimated using mixed-effect linear regression models. Separate estimates of the between (interpair and within (intrapair effects of each measure on development were thus obtained. Neurodevelopment was assessed with the Bayley Scales of Infant Development, 2nd edition, by a psychologist blind to the exposure. A standardized neurological examination was performed by a neuropediatrician who was unaware of the exposures under investigation. After adjustment, birth weight ratio and head circumference at birth were not associated with motor or mental outcomes. Current head circumference was associated with mental but not with motor outcomes. Only the intrapair twin effect was significant. An increase of 1 cm in current head circumference of one twin compared with the other was associated with 3.2 points higher in Mental Developmental Index (95%CI = 1.06-5.32; P < 0.03. Thus, no effect of intrauterine growth was found on cognition and only postnatal head growth was associated with cognition. This effect was not shared by the co-twin.

  7. The predictive validity of neonatal MRI for neurodevelopmental outcome in very preterm children.

    Science.gov (United States)

    Anderson, Peter J; Cheong, Jeanie L Y; Thompson, Deanne K

    2015-03-01

    Very preterm children are at a high risk for neurodevelopmental impairments, but there is variability in the pattern and severity of outcome. Neonatal magnetic resonance imaging (MRI) enhances the capacity to detect brain injury and altered brain development and assists in the prediction of high-risk children who warrant surveillance and early intervention. This review describes the application of conventional and advanced MRI with very preterm neonates, specifically focusing on the relationship between neonatal MRI findings and later neurodevelopmental outcome. Research demonstrates that conventional MRI is strongly associated with neurodevelopmental outcome in childhood. Further studies are needed to examine the role of advanced MRI techniques in predicting outcome in very preterm children, but early research findings are promising. In conclusion, neonatal MRI is predictive of later neurodevelopment but is dependent on appropriately trained specialists and should be interpreted in conjunction with other clinical and social information. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. An evaluation of speech production in two boys with neurodevelopmental disorders who received communication intervention with a speech-generating device.

    Science.gov (United States)

    Roche, Laura; Sigafoos, Jeff; Lancioni, Giulio E; O'Reilly, Mark F; Schlosser, Ralf W; Stevens, Michelle; van der Meer, Larah; Achmadi, Donna; Kagohara, Debora; James, Ruth; Carnett, Amarie; Hodis, Flaviu; Green, Vanessa A; Sutherland, Dean; Lang, Russell; Rispoli, Mandy; Machalicek, Wendy; Marschik, Peter B

    2014-11-01

    Children with neurodevelopmental disorders often present with little or no speech. Augmentative and alternative communication (AAC) aims to promote functional communication using non-speech modes, but it might also influence natural speech production. To investigate this possibility, we provided AAC intervention to two boys with neurodevelopmental disorders and severe communication impairment. Intervention focused on teaching the boys to use a tablet computer-based speech-generating device (SGD) to request preferred stimuli. During SGD intervention, both boys began to utter relevant single words. In an effort to induce more speech, and investigate the relation between SGD availability and natural speech production, the SGD was removed during some requesting opportunities. With intervention, both participants learned to use the SGD to request preferred stimuli. After learning to use the SGD, both participants began to respond more frequently with natural speech when the SGD was removed. The results suggest that a rehabilitation program involving initial SGD intervention, followed by subsequent withdrawal of the SGD, might increase the frequency of natural speech production in some children with neurodevelopmental disorders. This effect could be an example of response generalization. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  9. The effect of physician gender on length of patient consultations: observational findings from the UK hospital setting and synthesis with existing studies.

    Science.gov (United States)

    Jefferson, Laura; Bloor, Karen; Hewitt, Catherine

    2015-04-01

    To investigate the effect of physician gender on consultation length in UK hospital outpatient clinics and compare this, through meta-analysis, with previous studies outside the UK. Observational data on clinic times were analysed and findings were combined in a meta-analysis with existing studies investigating the effect of physician gender on consultation length. UK hospital practice. A total of 174 observations of outpatient consultations with 10 hospital specialists (consultants) from different specialties in two UK hospital trusts. Clinic times were recorded and analysis of consultation length was undertaken with physician gender as a covariate. Data were then synthesised through meta-analysis with 10 existing studies in this field. No statistically significant difference was found in the length of consultations for male and female doctors in these UK hospital settings. When pooled with existing studies, consultations with women doctors were found to be approximately two minutes longer than with men (p = 0.01). Findings from this analysis of clinic consultations in the UK National Health Service do not support previous studies, which were undertaken predominantly in North America and primary care settings. Overall, meta-analysis suggests doctors' gender may influence consultation length. Gender differences in communication should be considered in training clinicians and in overall clinical practice. © The Royal Society of Medicine.

  10. Amelioration of fetal alcohol-related neurodevelopmental disorders in rats: exploring pharmacological and environmental treatments.

    Science.gov (United States)

    Hannigan, J H; Berman, R F

    2000-01-01

    Fetal alcohol syndrome (FAS) and alcohol-related neurodevelopmental disorders (ARNDs) in children are characterized by life-long compromises in learning, memory, and adaptive responses. Until the advent of effective prevention measures, it will remain necessary to seek ways to treat the life-long neurobehavioral consequences of prenatal alcohol exposure. To date, there are no clinical remedies to recommend for either specific or global fetal alcohol effects. This article reviews our basic research in animal models that assesses the potential of global environmental manipulations or specific psychopharmacological treatments to ameliorate the neurobehavioral effects of prenatal exposure to alcohol. Postweaning environmental enrichment can improve behavioral performance and ameliorate or even eliminate deficits in prenatal alcohol-exposed rats, although there is persistent impairment in neuronal plasticity, as indicated by the failure of hippocampal pyramidal cells to increase dendrite spine density. Behavioral and neural responses to CNS stimulants differ in rats exposed prenatally to alcohol, although it is not clear that these shifts in dose-response curves would predict benefit to children. Although the present results may sound a note of optimism for the development of effective treatment strategies for children with FAS or ARNDs, it is important to consider that application of these findings in rodents may not be straightforward. We also need to know the critical features of specific environments that influence brain development, and the limits of pharmacotherapy, as well as critical periods of exposure. Continued study of the beneficial, ameliorative effects of environmental enrichment, rehabilitative training, and of pharmacological therapies in animal models, will remain a valuable source of information for eventually devising treatments specific for children with FAS and ARNDs.

  11. It does exist! A left-to-right spatial-numerical association of response codes (SNARC) effect among native Hebrew speakers.

    Science.gov (United States)

    Zohar-Shai, Bar; Tzelgov, Joseph; Karni, Avi; Rubinsten, Orly

    2017-04-01

    Several studies, starting with Dehaene, Bossini, and Giraux (1993), have reported that, in parity-judgment tasks, the difference in response latencies generated by the right and left hand are negatively correlated with number magnitudes. This SNARC (spatial-numerical association of response codes) effect is in line with the notion that the "mental number line" extends from left to right. The SNARC effect has been found mainly in native speakers of Germanic/Romanic languages; it has been suggested that the SNARC effect may derive from the experience of reading from left to right. To date, there is no evidence that the SNARC (or reverse SNARC) effect exists in parity judgments in native speakers of Hebrew readers. Here we provide the first demonstration of a horizontal, left-to-right SNARC effect in native speakers of Hebrew performing the parity task. Although we found no SNARC effect using the standard parity task, a reliable SNARC effect was found when we succeeded in reducing the MARC (markedness association of response codes) effect. We succeeded in reducing the MARC effect by implementing the parity task in 2 sessions, on 2 different days, each time using a different mapping of the parity-to-response side. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years after Initial Diagnosis

    Science.gov (United States)

    Gillberg, I. Carina; Helles, Adam; Billstedt, Eva; Gillberg, Christopher

    2016-01-01

    We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and followed up prospectively for almost two decades (13-26 years). Only three of the 50 men had "never" met criteria for an additional psychiatric/neurodevelopmental diagnosis and…

  13. Potential effects of existing and proposed groundwater withdrawals on water levels and natural groundwater discharge in Snake Valley and surrounding areas, Utah and Nevada

    Science.gov (United States)

    Masbruch, Melissa D.; Brooks, Lynette E.

    2017-04-14

    Several U.S. Department of Interior (DOI) agencies are concerned about the cumulative effects of groundwater development on groundwater resources managed by, and other groundwater resources of interest to, these agencies in Snake Valley and surrounding areas. The new water uses that potentially concern the DOI agencies include 12 water-right applications filed in 2005, totaling approximately 8,864 acre-feet per year. To date, only one of these applications has been approved and partially developed. In addition, the DOI agencies are interested in the potential effects of three new water-right applications (UT 18-756, UT 18-758, and UT 18-759) and one water-right change application (UT a40687), which were the subject of a water-right hearing on April 19, 2016.This report presents a hydrogeologic analysis of areas in and around Snake Valley to assess potential effects of existing and future groundwater development on groundwater resources, specifically groundwater discharge sites, of interest to the DOI agencies. A previously developed steady-state numerical groundwater-flow model was modified to transient conditions with respect to well withdrawals and used to quantify drawdown and capture (withdrawals that result in depletion) of natural discharge from existing and proposed groundwater withdrawals. The original steady-state model simulates and was calibrated to 2009 conditions. To investigate the potential effects of existing and proposed groundwater withdrawals on the groundwater resources of interest to the DOI agencies, 10 withdrawal scenarios were simulated. All scenarios were simulated for periods of 5, 10, 15, 30, 55, and 105 years from the start of 2010; additionally, all scenarios were simulated to a new steady state to determine the ultimate long-term effects of the withdrawals. Capture maps were also constructed as part of this analysis. The simulations used to develop the capture maps test the response of the system, specifically the reduction of natural

  14. Sequencing Chromosomal Abnormalities Reveals Neurodevelopmental Loci that Confer Risk across Diagnostic Boundaries

    DEFF Research Database (Denmark)

    Talkowski, Michael E.; Rosenfeld, Jill A.; Blumenthal, Ian

    2012-01-01

    Sequencing of balanced chromosomal abnormalities, combined with convergent genomic studies of gene expression, copy-number variation, and genome-wide association, identifies 22 new loci that contribute to autism and related neurodevelopmental disorders. These data support a polygenic risk model f...

  15. Child neurodevelopmental outcomes following preterm and term birth: What can the placenta tell us?

    Science.gov (United States)

    Hodyl, Nicolette A; Aboustate, Natalie; Bianco-Miotto, Tina; Roberts, Claire T; Clifton, Vicki L; Stark, Michael J

    2017-09-01

    A significant proportion of children born preterm will experience some level of neurodevelopmental impairment. Changes in placental function have been observed with many antenatal conditions that are risk factors for preterm birth and/or poor neurodevelopment including fetal growth restriction and in-utero inflammation. This review will highlight placental factors that have been studied to understand the underlying mechanisms and identify biomarkers that lead to poor child neurodevelopmental outcomes. These include changes in gross morphological and histopathological structure and the placental inflammatory response to prenatal infection. Further, we will describe the placenta's role as both a barrier to maternally-derived bioactive substances critical for normal fetal brain development, such as cortisol, and a source of neuroactive steroids and neurotrophins known to have critical functions in neuronal proliferation, axonal growth, myelination and the regulation of apoptosis. Finally, emerging data supporting the potential utility of novel placental biomarkers in the early prediction of poor neurodevelopmental outcome in infants born both preterm and term will be discussed. These include the assessment of genetic variants (e.g. single nucleotide polymorphisms in placental tissue) and epigenetic biomarkers (e.g. placental microRNAs and placental DNA methylation). With the placenta the key tissue regulating the fetal environment, integration of observed changes in placental function with genetic and epigenetic variations may advance our ability to predict future infant health. Ultimately, this may facilitate targeted allocation of health resources with the aim of improving lifelong neurodevelopmental capability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Neurodevelopmental Status and Adaptive Behaviors in Preschool Children with Chronic Kidney Disease

    Science.gov (United States)

    Duquette, Peter J.; Hooper, Stephen R.; Icard, Phil F.; Hower, Sarah J.; Mamak, Eva G.; Wetherington, Crista E.; Gipson, Debbie S.

    2009-01-01

    This study examines the early neurodevelopmental function of infants and preschool children who have chronic kidney disease (CKD). Fifteen patients with CKD are compared to a healthy control group using the "Mullen Scales of Early Learning" (MSEL) and the "Vineland Adaptive Behavior Scale" (VABS). Multivariate analysis reveals…

  17. Severe influenza among children and young adults with neurologic and neurodevelopmental conditions - Ohio, 2011.

    Science.gov (United States)

    2012-01-06

    Children with neurologic and neurodevelopmental conditions are at increased risk for severe outcomes from influenza, including death. In April 2011, the Ohio Department of Health and CDC investigated an influenza outbreak that began in February 2011 in a residential facility for 130 children and young adults with neurologic and neurodevelopmental conditions. This report summarizes the characteristics and clinical courses of 13 severely ill residents with suspected or confirmed influenza; 10 were hospitalized, and seven died. Diagnosis is challenging in this population, and clinicians should consider influenza in patients with neurologic and neurodevelopmental conditions who have respiratory illness or a decline in baseline medical status when influenza is circulating in the community. Prompt testing, early and aggressive antiviral treatment, and antiviral chemoprophylaxis are important for these patients. When influenza is suspected, antiviral treatment should be given as soon as possible after symptom onset, ideally within 48 hours. Treatment should not wait for laboratory confirmation of influenza. During outbreaks, antiviral chemoprophylaxis should be provided to all residents of institutional facilities (e.g., nursing homes and long-term- care facilities), regardless of vaccination status. Residential facilities for patients with neurologic and neurodevelopmental conditions are encouraged to vaccinate all eligible residents and staff members against influenza.

  18. Brain Injury and Neurodevelopmental Outcome in Congenital Heart Disease : A Systematic Review

    NARCIS (Netherlands)

    Mebius, Mirthe J.; Kool, Elisabeth M. W.; Bilardo, Catherina M.; Bos, Arend F.

    2017-01-01

    CONTEXT: Brain injury during prenatal and preoperative postnatal life might play a major role in neurodevelopmental impairment in infants with congenital heart disease (CIID) who require corrective or palliative surgery during infancy. A systematic review of cerebral findings during this period in

  19. Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy

    DEFF Research Database (Denmark)

    Mignot, Cyril; von Stülpnagel, Celina; Nava, Caroline

    2016-01-01

    OBJECTIVE: We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype-phenotype correlations. METHODS: We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular and clini......OBJECTIVE: We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype-phenotype correlations. METHODS: We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular...... and clinical data from patients with SYNGAP1 mutations from other centres were also collected, focusing on developmental aspects and the associated epilepsy phenotype. A review of SYNGAP1 mutations published in the literature was also performed. RESULTS: We describe 17 unrelated affected individuals carrying...... 13 different novel loss-of-function SYNGAP1 mutations. Developmental delay was the first manifestation of SYNGAP1-related encephalopathy; intellectual disability became progressively obvious and was associated with autistic behaviours in eight patients. Hypotonia and unstable gait were frequent...

  20. Lessons Learned: Engaging Culturally Diverse Families in Neurodevelopmental Disorders Intervention Research

    Science.gov (United States)

    Ratto, Allison B.; Anthony, Bruno J.; Pugliese, Cara; Mendez, Rocio; Safer-Lichtenstein, Jonathan; Dudley, Katerina M.; Kahn, Nicole F.; Kenworthy, Lauren; Biel, Matthew; Martucci, Jillian L.; Anthony, Laura G.

    2017-01-01

    Low-income and ethnic minority families continue to face critical disparities in access to diagnostic and treatment services for neurodevelopmental conditions, such as autism spectrum disorder and attention deficit hyperactivity disorder. Despite the growing cultural diversity of the United States, ethnic minority children and families continue to…

  1. Neurobiological Circuits Regulating Attention, Cognitive Control, Motivation, and Emotion: Disruptions in Neurodevelopmental Psychiatric Disorders

    Science.gov (United States)

    Arnsten, Amy F. T.; Rubia, Katya

    2012-01-01

    Objective: This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Method: Studies of animals,…

  2. Communication Intervention for Young Children with Severe Neurodevelopmental Disabilities via Telehealth

    Science.gov (United States)

    Simacek, Jessica; Dimian, Adele F.; McComas, Jennifer J.

    2017-01-01

    Young children with neurodevelopmental disorders such as autism spectrum disorders (ASD) and Rett syndrome often experience severe communication impairments. This study examined the efficacy of parent-implemented communication assessment and intervention with remote coaching via telehealth on the acquisition of early communication skills of three…

  3. Midazolam dose correlates with abnormal hippocampal growth and neurodevelopmental outcome in preterm infants.

    Science.gov (United States)

    Duerden, Emma G; Guo, Ting; Dodbiba, Lorin; Chakravarty, M Mallar; Chau, Vann; Poskitt, Kenneth J; Synnes, Anne; Grunau, Ruth E; Miller, Steven P

    2016-04-01

    Very preterm-born neonates (24-32 weeks of gestation) are exposed to stressful and painful procedures during neonatal intensive care. Analgesic and sedation therapies are essential, and opiates and benzodiazepines are commonly used. These medications may negatively impact brain development. The hippocampus may be especially vulnerable to the effects of pain and analgesic and/or sedative therapies and contribute to adverse outcomes. The effect of invasive procedures and analgesic-sedative exposure on hippocampal growth was assessed, as was that of hippocampal growth on neurodevelopmental outcome. A total of 138 neonates (51% male, median gestational age = 27.7 weeks) underwent magnetic resonance imaging and diffusion tensor imaging (DTI) scans, early in life (postmenstrual age [PMA] = 32.3 weeks) and at term-equivalent age (PMA = 40.2 weeks). Volumes and DTI measures of axial diffusivity, radial diffusivity, and mean diffusivity (MD) were obtained from the hippocampus. Cognitive, language, and motor abilities were assessed using the Bayley Scales of Infant Development-III at 18.7 months median corrected age. Models testing the association of invasive procedures with hippocampal volumes and DTI measures accounted for birth gestational age, sex, PMA, dose of analgesics/sedatives (fentanyl, morphine, midazolam), mechanical ventilation, hypotension, and surgeries. Total midazolam dose predicted decreased hippocampal volumes (β = -1.8, p 0.5 each). Lower cognitive scores were associated with hippocampal growth (β = -0.31, p = 0.003), midazolam dose (β = -0.27, p = 0.03), and surgery (β = -8.32, p = 0.04). Midazolam exposure was associated with macro- and microstructural alterations in hippocampal development and poorer outcomes consistent with hippocampal dysmaturation. Use of midazolam in preterm neonates, particularly those not undergoing surgery, is cautioned. © 2016 American Neurological Association.

  4. Effect of pre-existing maternal obesity, gestational diabetes and adipokines on the expression of genes involved in lipid metabolism in adipose tissue.

    Science.gov (United States)

    Lappas, Martha

    2014-02-01

    To determine the effect of maternal obesity, gestational diabetes mellitus (GDM) and adipokines on the expression of genes involved in fatty acid uptake, transport, synthesis and metabolism. Human subcutaneous and omental adipose tissues were obtained from lean, overweight and obese normal glucose tolerant (NGT) women and women with GDM. Quantitative RT-PCR (qRT-PCR) was performed to determine the level of expression. Adipose tissue explants were performed to determine the effect of the adipokines TNFα, IL-1β and leptin on adipose tissue gene expression. Pre-existing maternal obesity and GDM are associated with decreased expression in genes involved in fatty acid uptake and intracellular transport (LPL, FATP2, FATP6, FABPpm and ASCL1), triacylglyceride (TAG) biosynthesis (MGAT1,7 MGAT2 and DGAT1), lipogenesis (FASN) and lipolysis (PNPLA2, HSL and MGLL). Decreased gene expression was also observed for the transcription factors involved in lipid metabolism (LXRα, PPARα, PPARδ, PPARγ, RXRα and SREBP1c). On the other hand, the gene expression of the adipokines TNFα, IL-1β and or leptin was increased in adipose tissue from obese and GDM women. Functional in vitro studies revealed that these adipokines decreased the gene expression of LPL, FATP2, FATP6, ASCL1, PNPLA2, PPARδ, PPARγ and RXRα. Pregnancies complicated by pre-existing maternal obesity and GDM are associated with abnormal adipose tissue lipid metabolism, which may play a role in the pathogenesis of these diseases. © 2014.

  5. Early neurodevelopmental screening in tuberous sclerosis complex: a potential window of opportunity.

    Science.gov (United States)

    Gipson, Tanjala T; Gerner, Gwendolyn; Srivastava, Siddharth; Poretti, Andrea; Vaurio, Rebecca; Hartman, Adam; Johnston, Michael V

    2014-09-01

    Infants born with tuberous sclerosis complex, a genetic condition resulting from a mutation in TSC1 or TSC2, are at increased risk for intellectual disability and/or autism. Features of epilepsy, neuropathology, genetics, as well as timing and type of mechanism-based medications have been proposed as risk factors. Neurodevelopmental outcomes have been reported among these studies; however, few include data about the individuals' early neurodevelopmental profile, a factor that may contribute significantly to these outcomes. Further, there is no clinical standard for the neurodevelopmental assessment of these infants. The paucity of data regarding the natural history of neurodevelopment in infants with tuberous sclerosis complex and the lack of a gold standard for neurodevelopmental evaluation present a significant challenge for clinicians and researchers. During the first year of life, we tracked the onset of infantile spasms, the type and timing of antiepileptic treatments, and the associated response of two age-matched infants with tuberous sclerosis complex. We also employed Capute Scales as a part of a structured neurodevelopmental evaluation to characterize and compare their neurodevelopmental profiles. Infant 1 developed infantile spasms with confirmed hypsarrhythmia at 4 months of age. Treatment with vigabatrin was initiated within 24 hours with near immediate cessation of seizures and no further seizures to date. Expressive language delay was detected at 12 months and treated with speech and/or language therapy. Infant 2 developed complex partial seizures at 1 month. Treatment included levetiracetam, oxcarbazepine, and the ketogenic diet. Vigabatrin was initiated on detection of hypsarrhythmia after 4 months. Intractable epilepsy persists to date. Global developmental delay was evident by 8 months and treated with physical, occupational, and speech and/or language therapy. Many risk factors have been associated with intellectual disability and/or autism in

  6. The EXIST OIRT

    Science.gov (United States)

    Allen, Branden; Golisano, C.; Kutyrev, A.; Moseley, H.; Grindlay, J.; Hong, J.; EXIST Team

    2009-01-01

    The EXIST Optical / Infrared Telescope (OIRT) has been integrated into the EXIST concept design for the determination GRB redshifts on orbit and to preform follow up source identification and studies following the generation of a trigger from the EXIST high energy telescope (HET). The base OIRT main design has been inherited from the NextView OIRT has been operating in low earth orbit since September of 2007 and is currently being used for the acquisition of geospatial data. After reconfiguration of the instrumentation for astrophysical observations the OIRT will have an angular resolution of 0.15" and a 5'×5' field of view and be sensitive to emission in the range of 0.4 $\\mu$m - 2.2 $\\mu$m. Passive cooling of the tertiary, secondary, and primary mirrors will enable observation into the Ks$ band.

  7. The effects of aerobic- versus strength-training on body image among young women with pre-existing body image concerns.

    Science.gov (United States)

    Martin Ginis, Kathleen A; Strong, Heather A; Arent, Shawn M; Bray, Steven R; Bassett-Gunter, Rebecca L

    2014-06-01

    This experiment compared the effects of aerobic-training (AT) versus strength-training (ST) on body image among young women with pre-existing body image concerns. Theory-based correlates of body image change were also examined. Participants were 46 women (M age=21.5 years), randomly assigned to an 8-week AT or ST intervention consisting of supervised exercise 3 days/week. Multidimensional measures of body image were administered pre- and post-intervention, along with measures of physical fitness, perceived fitness, and exercise self-efficacy. Women in the AT condition reported greater reductions in social physique anxiety (p=.001) and tended to report greater improvements in appearance evaluation (p=.06) than women in the ST condition. Changes in perceived fatness, perceived aerobic endurance and aerobic self-efficacy were significantly correlated with body image change (psbody image and advancing theory to account for the effects of exercise. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Neurodevelopmental functioning in children with FAS, pFAS, and ARND.

    Science.gov (United States)

    Chasnoff, Ira J; Wells, Anne M; Telford, Erin; Schmidt, Christine; Messer, Gwendolyn

    2010-04-01

    The purpose of this article is to compare the neurodevelopmental profiles of 78 foster and adopted children with fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND). Seventy-eight foster and adopted children underwent a comprehensive diagnostic evaluation. By using criteria more stringent than those required by current guidelines, the children were placed in 1 of 3 diagnostic categories: FAS, pFAS, or ARND. Each child was evaluated across the domains of neuropsychological functioning most frequently affected by prenatal exposure to alcohol. Multivariate analyses of variance were conducted to examine differences in neuropsychological functioning between the 3 diagnostic groups. Descriptive discriminant analyses were performed in follow-up to the multivariate analyses of variance. The children in the 3 diagnostic categories were similar for descriptive and child welfare variables. Children with FAS had significantly decreased mean weight, height, and head circumference. Children with FAS exhibited the most impaired level of general intelligence, significantly worse language-based memory compared with children with ARND, and significantly poorer functional communication skills than children with pFAS. On executive functioning, the FAS group of children performed significantly worse on sequencing and shift than either the pFAS or ARND groups. Children with pFAS and ARND were similar in all neurodevelopmental domains that were tested. The children who met tightly defined physical criteria for a diagnosis of FAS demonstrated significantly poorer neurodevelopmental functioning than children with pFAS and ARND. Children in these latter 2 groups were similar in all neurodevelopmental domains that were tested.

  9. Telephone interviews and online questionnaires can be used to improve neurodevelopmental follow-up rates.

    Science.gov (United States)

    Johnson, Samantha; Seaton, Sarah E; Manktelow, Bradley N; Smith, Lucy K; Field, David; Draper, Elizabeth S; Marlow, Neil; Boyle, Elaine M

    2014-04-08

    Maximising response rates to neurodevelopmental follow-up is a key challenge for paediatric researchers. We have investigated the use of telephone interviews and online questionnaires to improve response rates, reduce non-response bias, maintain data completeness and produce unbiased outcomes compared with postal questionnaires when assessing neurodevelopmental outcomes at 2 years. A prospective cohort study of babies born ≥32 weeks gestation. Neurodevelopmental outcomes were assessed at 2 years of age using a parent questionnaire completed via post, telephone or online. Relative Risks with 95% confidence intervals (RR; 95% CI) were calculated to identify participant characteristics associated with non-response and questionnaire response mode (postal vs. telephone/online). The proportion of missing data and prevalence of adverse outcomes was compared between response modes using generalized linear models. Offering telephone/online questionnaires increased the study response rate from 55% to 60%. Telephone/online responders were more likely to be non-white (RR 1.6; [95% CI 1.1, 2.4]), non-English speaking (1.6; [1.0, 2.6]) or have a multiple birth (1.6; [1.1, 2.3]) than postal responders. There were no significant differences in the prevalence of adverse neurodevelopmental outcomes between those who responded via post vs. telephone/online (1.1; [0.9, 1.4]). Where parents attempted all questionnaire sections, there were no significant differences in the proportion of missing data between response modes. Where there is sufficient technology and resources, offering telephone interviews and online questionnaires can enhance response rates and improve sample representation to neurodevelopmental follow-up, whilst maintaining data completeness and unbiased outcomes.

  10. Automated electroencephalographic discontinuity in cooled newborns predicts cerebral MRI and neurodevelopmental outcome.

    Science.gov (United States)

    Dunne, Jonathan M; Wertheim, David; Clarke, Paul; Kapellou, Olga; Chisholm, Philippa; Boardman, James P; Shah, Divyen K

    2017-01-01

    Prolonged electroencephalographic (EEG) discontinuity has been associated with poor neurodevelopmental outcomes after perinatal asphyxia but its predictive value in the era of therapeutic hypothermia (TH) is unknown. In infants undergoing TH for hypoxic-ischaemic encephalopathy (HIE) prolonged EEG discontinuity is associated with cerebral tissue injury on MRI and adverse neurodevelopmental outcome. Retrospective study of term neonates from three UK centres who received TH for perinatal asphyxia, had continuous two channel amplitude-integrated EEG with EEG for a minimum of 48 h, brain MRI within 6 weeks of birth and neurodevelopmental outcome data at a median age of 24 months. Mean discontinuity was calculated using a novel automated algorithm designed for analysis of the raw EEG signal. Of 49 eligible infants, 17 (35%) had MR images predictive of death or severe neurodisability (unfavourable outcome) and 29 (59%) infants had electrographic seizures. In multivariable logistic regression, mean discontinuity at 24 h and 48 h (both p=0.01), and high seizure burden (p=0.05) were associated with severe cerebral tissue injury on MRI. A mean discontinuity >30 s/min-long epoch, had a specificity and positive predictive value of 100%, sensitivity of 71% and a negative predictive value of 88% for unfavourable neurodevelopmental outcome at a 10 µV threshold. In addition to seizure burden, excessive EEG discontinuity is associated with increased cerebral tissue injury on MRI and is predictive of abnormal neurodevelopmental outcome in infants treated with TH. The high positive predictive value of EEG discontinuity at 24 h may be valuable in selecting newborns with HIE for adjunctive treatments. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Does Unconscious Racism Exist?

    Science.gov (United States)

    Quillian, Lincoln

    2008-01-01

    This essay argues for the existence of a form of unconscious racism. Research on implicit prejudice provides good evidence that most persons have deeply held negative associations with minority groups that can lead to subtle discrimination without conscious awareness. The evidence for implicit attitudes is briefly reviewed. Criticisms of the…

  12. Mice lacking Brinp2 or Brinp3, or both, exhibit behaviours consistent with neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Susie Ruth Berkowicz

    2016-10-01

    Full Text Available Background: Brinps 1 – 3, and Astrotactins (Astn 1 and 2, are members of the Membrane Attack Complex / Perforin (MACPF superfamily that are predominantly expressed in the mammalian brain during development. Genetic variation at the human BRINP2/ASTN1 and BRINP1/ASTN2 loci has been implicated in neurodevelopmental disorders. We, and others, have previously shown that Brinp1-/- mice exhibit behaviour reminiscent of autism spectrum disorder (ASD and attention deficit hyperactivity disorder (ADHD.Method: We created Brinp2-/- mice and Brinp3-/- mice via the Cre-mediated LoxP system to investigate the effect of gene deletion on anatomy and behaviour. Additionally, Brinp2-/-Brinp3-/- double knock-out mice were generated by interbreeding Brinp2-/- and Brinp3-/- mice. Genomic validation was carried out for each knock-out line, followed by histological, weight and behavioural examination. Brinp1-/-Brinp2-/-Brinp3-/- triple knock-out mice were also generated by crossing Brinp2/3 double knock-out mice with previously generated Brinp1-/- mice, and examined by weight and histological analysis.Results: Brinp2-/- and Brinp3-/- mice differ in their behaviour: Brinp2-/- mice are hyperactive, whereas Brinp3-/- mice exhibit marked changes in anxiety-response on the elevated plus maze. Brinp3-/- mice also show evidence of altered sociability. Both Brinp2-/- and Brinp3-/- mice have normal short-term memory, olfactory responses, pre-pulse inhibition and motor learning. The double knock-out mice show behaviours of Brinp2-/- and Brinp3-/- mice, without evidence of new or exacerbated phenotypes. Conclusion: Brinp3 is important in moderation of anxiety, with potential relevance to anxiety disorders. Brinp2 dysfunction resulting in hyperactivity may be relevant to the association of ADHD with chromosome locus 1q25.2. Brinp2-/- and Brinp3-/- genes do not compensate in the mammalian brain and likely have distinct molecular or cell-type specific functions.

  13. Fiber mediated receptor masking in non-infected bystander cells restricts adenovirus cell killing effect but promotes adenovirus host co-existence.

    Directory of Open Access Journals (Sweden)

    Johan Rebetz

    Full Text Available The basic concept of conditionally replicating adenoviruses (CRAD as oncolytic agents is that progenies generated from each round of infection will disperse, infect and kill new cancer cells. However, CRAD has only inhibited, but not eradicated tumor growth in xenograft tumor therapy, and CRAD therapy has had only marginal clinical benefit to cancer patients. Here, we found that CRAD propagation and cancer cell survival co-existed for long periods of time when infection was initiated at low multiplicity of infection (MOI, and cancer cell killing was inefficient and slow compared to the assumed cell killing effect upon infection at high MOI. Excessive production of fiber molecules from initial CRAD infection of only 1 to 2% cancer cells and their release prior to the viral particle itself caused a tropism-specific receptor masking in both infected and non-infected bystander cells. Consequently, the non-infected bystander cells were inefficiently bound and infected by CRAD progenies. Further, fiber overproduction with concomitant restriction of adenovirus spread was observed in xenograft cancer therapy models. Besides the CAR-binding Ad4, Ad5, and Ad37, infection with CD46-binding Ad35 and Ad11 also caused receptor masking. Fiber overproduction and its resulting receptor masking thus play a key role in limiting CRAD functionality, but potentially promote adenovirus and host cell co-existence. These findings also give important clues for understanding mechanisms underlying the natural infection course of various adenoviruses.

  14. Investigation of the Effects of rs137852599 Single-nucleotide Polymorphism Existence in Drug Resistance against Treatment with Enzalutamide in Individuals Diagnosed with Prostate Cancer in Isfahan Province

    Directory of Open Access Journals (Sweden)

    Bita Kaviani

    2018-02-01

    Full Text Available Abstract Background: The aim of this study is to investigate the role of rs137852599 single-nucleotide polymorphism in the androgen receptor coding gene on drug resistance against treatment with Enzalutamide in individuals diagnosed with prostate cancer. Materials and Methods: In this case-control study, the ARMS-PCR analysis was conducted on androgen receptor coding gene in 50 patients diagnosed with prostate cancer with drug resistance and on 50 patients diagnosed with prostate cancer without drug resistance. The statistical analyses were performed using the GeNePop server and then the results were investigated by the SISA server. Results: The allele frequencies of A and C alleles in rs137852599 were 0.78 and 0.22 for drug resistant and 0.94 and 0.06 for non-drug resistance groups. The results indicated that there is a meaningful relationship between drug resistance and rs137852599 single-nucleotide polymorphism (p = 0.020. Conclusion: The existence of single-nucleotide polymorphisms may result in drug resistance in individuals diagnosed with prostate cancer. Therefore, investigation of the existence of such polymorphisms can be effective in prescription of suitable drugs for these patients.

  15. Children with neurodevelopmental disorders and disabilities: a population-based study of healthcare service utilization using administrative data.

    Science.gov (United States)

    Arim, Rubab G; Miller, Anton R; Guèvremont, Anne; Lach, Lucyna M; Brehaut, Jamie C; Kohen, Dafna E

    2017-12-01

    The aim of this study was to identify children with neurodevelopmental disorders and disabilities (NDD/D) and compare their healthcare service utilization to children without NDD/D using provincial linked administrative data. The sample included children aged 6 to 10 years (n=183 041), who were registered with the British Columbia Medical Services Plan. Diagnostic information was used for the identification and classification of NDD/D in six functional domains. Healthcare service utilization included outcomes based on physician claims, prescription medication use, and hospitalization. Overall, 8.3% of children were identified with NDD/D. Children with NDD/D had higher healthcare service utilization rates than those without NDD/D. Effect sizes were: very large for the number of days a prescription medication was dispensed; large for the number of prescriptions; medium for the number of physician visits, different specialists visited, number of different prescription medications, and ever hospitalized; and small for the number of laboratory visits, X-ray visits, and number of days hospitalized. The findings have policy implications for service and resource planning. Given the high use of psychostimulants, specialized services for both NDD/D and psychiatric conditions may be the most needed services for children with NDD/D. Future studies may examine patterns of physician behaviours and costs attributable to healthcare service utilization for children with NDD/D. Children with neurodevelopmental disorders and disabilities (NDD/D) have higher healthcare service utilization than those without. Based on provincial population-based linked administrative health data, a sizeable number of children are living with NDD/D. Given the high use of psychostimulants, specialized services for children with both NDD/D and psychiatric conditions may be the most needed services for children with NDD/D. © 2017 Mac Keith Press.

  16. “Selfish spermatogonial selection”: a novel mechanism for the association between advanced paternal age and neurodevelopmental disorders

    Science.gov (United States)

    Goriely, Anne; McGrath, John J.; Hultman, Christina M.; Wilkie, Andrew O.M.; Malaspina, Dolores

    2014-01-01

    Objectives There is robust evidence from epidemiological studies that the offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism. Here we present a novel mechanism that may contribute to this association. Methods Narrative review. Results Because the male germ cell undergoes many more cell divisions across the reproductive age range, copy-errors taking place in the paternal germline are associated with de novo mutations in the offspring of older men. Recently it has been recognized that somatic mutations in male germ cells that modify proliferation via dysregulation of the RAS pathway can lead to within-testis expansion of mutant clonal lines. First identified in association with rare paternal age-effect disorders (e.g. Apert syndrome, achondroplasia), this process is known as ‘selfish spermatogonial selection’. This mechanism will (a) favor propagation of germ cells carrying pathogenic mutations, (b) increasingly skew the mutational profile of sperm as men age, and (c) result in an enrichment of de novo mutations in the offspring of older fathers that preferentially impact on specific cellular signaling pathways. This mechanism offers a parsimonious explanation not only for the association between advanced paternal age and various neurodevelopmental disorders, but also provides insights into the genetic architecture (role of de novo mutations), neurobiological correlates (altered cell cycle) and some epidemiological features of these disorders. We outline hypotheses to test this model. Conclusions In light of our current understanding of the genetic networks involved in neurocognitive disorders and the principles of selfish spermatogonial selection, we speculate that some pathogenic mutations associated with these disorders are the consequence of a selfish mechanism originating in the aging testis. Given the secular changes for delayed parenthood in most societies, this hypothesis has important public

  17. Effects of Starvation and Thermal Stress on the Thermal Tolerance of Silkworm, Bombyx mori: Existence of Trade-offs and Cross-Tolerances.

    Science.gov (United States)

    Mir, A H; Qamar, A

    2017-09-27

    Organisms, in nature, are often subjected to multiple stressors, both biotic and abiotic. Temperature and starvation are among the main stressors experienced by organisms in their developmental cycle and the responses to these stressors may share signaling pathways, which affects the way these responses are manifested. Temperature is a major factor governing the performance of ectothermic organisms in ecosystems worldwide and, therefore, the thermal tolerance is a central issue in the thermobiology of these organisms. Here, we investigated the effects of starvation as well as mild heat and cold shocks on the thermal tolerance of the larvae of silkworm, Bombyx mori (Linnaeus). Starvation acted as a meaningful or positive stressor as it improved cold tolerance, measured as chill coma recovery time (CCRT), but, at the same time, it acted as a negative stressor and impaired the heat tolerance, measured as heat knockdown time (HKT). In the case of heat tolerance, starvation negated the positive effects of both mild cold as well as mild heat shocks and thus indicated the existence of trade-off between these stressors. Both mild heat and cold shocks improved the thermal tolerance, but the effects were more prominent when the indices were measured in response to a stressor of same type, i.e., a mild cold shock improved the cold tolerance more than the heat tolerance and vice versa. This improvement in thermal tolerance by both mild heat as well as cold shocks indicated the possibility of cross-tolerance between these stressors.

  18. A novel research design can aid disinvestment from existing health technologies with uncertain effectiveness, cost-effectiveness, and/or safety.

    Science.gov (United States)

    Haines, Terry; O'Brien, Lisa; McDermott, Fiona; Markham, Donna; Mitchell, Deb; Watterson, Dina; Skinner, Elizabeth

    2014-02-01

    Disinvestment is critical for ensuring the long-term sustainability of health-care services. Key barriers to disinvestment are heterogeneity between research and clinical settings, absence of evidence of effectiveness of some health technologies, and exposure of patients and organizations to risks and poor outcomes. We aimed to develop a feasible research design that can evaluate disinvestment in health technologies of uncertain effectiveness or cost-effectiveness. This article (1) establishes the need for disinvestment methodologies, (2) identifies the ethical concerns and feasibility constraints of conventional research designs for this issue, (3) describes the planning, implementation, and analytical framework for a novel disinvestment-specific study design, and (4) describes potential limitations in application of this design. The stepped-wedge, roll-in cluster randomized controlled trial can facilitate the disinvestment process, whereas generating evidence to determine whether the decision to disinvest was sound in the clinical environment. A noninferiority research paradigm may be applied to this methodology to demonstrate that the removal of a health technology does not adversely affect outcomes. This research design can be applied across multiple fields and will assist determination of whether specific health technologies are clinically effective, cost-effective, and safe. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Existing chemicals: international activities.

    Science.gov (United States)

    Purchase, J F

    1989-01-01

    The standards of care used in the protection of the health and safety of people exposed to chemicals has increased dramatically in the last decade. Standards imposed by regulation and those adopted by industry have required a greater level of knowledge about the hazards of chemicals. In the E.E.C., the 6th amendment of the dangerous substances directive imposed the requirement that al new chemicals should be tested according to prescribed programme before introduction on to the market. The development of a European inventory of existing chemicals was an integral part of the 6th amendment. It has now become clear that increased standards of care referred to above must be applied to the chemicals on the inventory list. There is, however, a considerable amount of activity already under way in various international agencies. The OECD Chemicals Programme has been involved in considering the problem of existing chemicals for some time, and is producing a priority list and action programme. The International Programme on Chemical Safety produces international chemical safety cards, health and safety guides and environmental health criteria documents. The international register of potentially toxic compounds (part of UNEP) has prepared chemical data profiles on 990 compounds. The International Agency for Research on Cancer prepared monographs on the carcinogenic risk of chemicals to man. So far 42 volumes have been prepared covering about 900 substances. IARC and IPCS also prepare periodic reports on ongoing research on carcinogenicity or toxicity (respectively) of chemicals. The chemical industry through ECETOC (the European Chemical Industry Ecology and Toxicology Centre) has mounted a major initiative on existing chemicals. Comprehensive reviews of the toxicity of selected chemicals are published (Joint Assessment of Commodity Chemicals). In its technical report no. 30 ECETOC lists reviews and evaluations by major national and international organisations, which provides

  20. Do multiquark hadrons exist

    Energy Technology Data Exchange (ETDEWEB)

    Weinstein, J.; Isgur, N.

    1982-03-08

    The qqq-barq-bar system has been examined by solving the four-particle Schroedinger equation variationally. The main findings are that: (1) qqq-barq-bar bound states normally do not exist, (2) the cryptoexotic 0/sup + +/ sector of this system with KK-bar quantum numbers is probably the only exception to (1) and its bound states can be identified with the S* and delta just below KK-bar threshold, (3) qqq-barq-bar bound states provide a model for the weak binding and color-singlet clustering observed in nuclei, and (4) there is no indication that this system has strong resonances.

  1. The Perfect Storm: Preterm Birth, Neurodevelopmental Mechanisms, and Autism Causation.

    Science.gov (United States)

    Erdei, Carmina; Dammann, Olaf

    2014-01-01

    A unifying model of autism causation remains elusive, and thus well-designed explanatory models are needed to develop appropriate therapeutic and preventive interventions. This essay argues that autism is not a static disorder, but rather an ongoing process. We discuss the link between preterm birth and autism and briefly review the evidence supporting the link between immune system characteristics and both prematurity and autism. We then propose a causation process model of autism etiology and pathogenesis, in which both neurodevelopment and ongoing/prolonged neuroinflammation are necessary pathogenetic component mechanisms. We suggest that an existing model of sufficient cause and component causes can be interpreted as a mechanistic view of etiology and pathogenesis and can serve as an explanatory model for autism causal pathways.

  2. Repowering existing plants

    Energy Technology Data Exchange (ETDEWEB)

    Steazel, W.C.; Sopocy, D.M.; Pace, S.E.

    1998-07-01

    Increased competition among power generation companies, changes in generating system load requirements, lower allowable plant emissions, and changes in fuel availability and cost accentuate the need to closely assess the economics and performances of older electric generation units. Generally, decisions must be made as to whether these units should be retired and replaced with new generation capacity, whether capacity should be purchased from other generation companies, or if these existing units should be repowered. These decisions usually require the evaluation of many factors including; environmental discharge limits, permitting requirements, generating load demand increases, options for increasing the benefits of using existing facilities (e.g.; increasing efficiency and output), fuel cost increases, transmission requirements and access, optional plant designs. Many of these factors need to be used in the analysis based on a range rather than one specific value to test for changes in the selection of the best option because of future uncertainties. Usually complicated analysis results because of all the factors involved. Computer products that integrate performance and financial analysis can provide substantial value by enabling the user to evaluate the applicable plant options and range of input. The SOAPP (State-of-the-Art Power Plant) family of software products provides easy to use tools for rapid, thorough and economical evaluation of plant option. Repowering evaluation methodology typically used in the US, technology options, and available SOAPP repowering software are reviewed in this paper.

  3. Effects of adding a new PCMH block rotation and resident team to existing longitudinal training within a certified PCMH: primary care residents' attitudes, knowledge, and experience.

    Science.gov (United States)

    Anandarajah, Gowri; Furey, Christopher; Chandran, Rabin; Goldberg, Arnold; El Rayess, Fadya; Ashley, David; Goldman, Roberta E

    2016-01-01

    Although the patient-centered medical home (PCMH) model is considered important for the future of primary care in the USA, it remains unclear how best to prepare trainees for PCMH practice and leadership. Following a baseline study, the authors added a new required PCMH block rotation and resident team to an existing longitudinal PCMH immersion and didactic curriculum within a Level 3-certified PCMH, aiming for "enhanced situated learning". All 39 residents enrolled in a USA family medicine residency program during the first year of curricular implementation completed this new 4-week rotation. This study examines the effects of this rotation after 1 year. A total of 39 intervention and 13 comparison residents were eligible participants. This multimethod study included: 1) individual interviews of postgraduate year (PGY) 3 intervention vs PGY3 comparison residents, assessing residents' PCMH attitudes, knowledge, and clinical experience, and 2) routine rotation evaluations. Interviews were audiorecorded, transcribed, and analyzed using immersion/crystallization. Rotation evaluations were analyzed using descriptive statistics and qualitative analysis of free text responses. Authors analyzed 23 interviews (88%) and 26 rotation evaluations (67%). Intervention PGY3s' interviews revealed more nuanced understanding of PCMH concepts and more experience with system-level PCMH tasks than those of comparison PGY3s. More intervention PGY3s rated themselves "extremely prepared" to implement PCMH than comparison PGY3s; however, most self-rated "somewhat prepared". Their reflections demonstrated deeper understanding of PCMH implementation and challenges than comparison PGY3s but inadequate experience to directly see the results of successful solutions. Rotation evaluations from PGY1, PGY2, and PGY3s revealed strengths and several areas for improvement. Adding one 4-week block rotation to existing longitudinal training appears to improve residents' PCMH knowledge, skills, and

  4. Neurodevelopmental disorders: theoretical approaches and its implications for education and rehabilitation

    Directory of Open Access Journals (Sweden)

    Maria Luísa Bissoto

    2011-06-01

    Full Text Available The neurodevelopmental disorders, mainly those genetics ones, are argued with the aim to analyze the human development conceptions that underlie these, and its impact for understanding who is the individual that carries this disorder. Methodologically, epistemological presupposition from “classical” neuropsychology and from “neuroconstructivist” neuropsychology had been compared. As results of this parallel had been considered relevant: a. the role of the individual surrounding, b. the question concerning the plasticity and dynamical character of development and c. the formal developmental process, from prenatal to postnatal period. The concluding comments claims that the Neuroconstructivist approaches allow conceiving the developmental process within genetics neurodevelopmental disorders not as a “fault” but as a differentiated and particular one. That should be understood in the Educational and Rehabilitation settings not as a nosological category but as a specific way of an individual acting while looking for a mode of being-in-the-world.

  5. Expression of human Gaucher disease gene GBA generates neurodevelopmental defects and ER stress in Drosophila eye.

    Directory of Open Access Journals (Sweden)

    Takahiro Suzuki

    Full Text Available Gaucher disease (GD is the most common of the lysosomal storage disorders and is caused by defects in the GBA gene encoding glucocerebrosidase (GlcCerase. The accumulation of its substrate, glucocylceramide (GlcCer is considered the main cause of GD. We found here that the expression of human mutated GlcCerase gene (hGBA that is associated with neuronopathy in GD patients causes neurodevelopmental defects in Drosophila eyes. The data indicate that endoplasmic reticulum (ER stress was elevated in Drosophila eye carrying mutated hGBAs by using of the ER stress markers dXBP1 and dBiP. We also found that Ambroxol, a potential pharmacological chaperone for mutated hGBAs, can alleviate the neuronopathic phenotype through reducing ER stress. We demonstrate a novel mechanism of neurodevelopmental defects mediated by ER stress through expression of mutants of human GBA gene in the eye of Drosophila.

  6. Phenotypic plasticity and the perception-action-cognition-environment paradigm in neurodevelopmental genetic disorders.

    Science.gov (United States)

    Dan, Bernard; Pelc, Karine; de Meirleir, Linda; Cheron, Guy

    2015-04-01

    Careful study of the phenotype can have implications at several levels, namely clinical diagnosis, pathophysiological reasoning, management planning, and outcome measurement. Behavioural phenotypes involve cognition, communication, social skills, and motor control. They can be documented in a host of neurodevelopmental conditions and approached with the recently refined perception-action-cognition-environment (PACE) paradigm, which focuses on the neurodevelopmental processes that underlie learning and adaption to the environment through perception, action, and cognitive processing. Although this paradigm was originally developed in the context of cerebral palsy, it can be applied along developmental trajectories in several neurogenetic conditions, including Down syndrome, fragile X syndrome, Rett syndrome, Angelman syndrome, and Williams syndrome, to name but a few. It must be recognized, however, that relevant, valid tools for assessment and management strategies still need to be developed. © 2015 The Authors. Developmental Medicine & Child Neurology © 2015 Mac Keith Press.

  7. Existence of Minkowski space

    CERN Document Server

    Wagner, Serge

    2016-01-01

    Physics textbooks present Minkowski space as an almost pure mathematical construct, without any explicit restriction on a domain where it is applicable in physics. Meanwhile, its physical meaning cannot but follow the same premises as those which underlies the special relativity theory: motion of free point particles and propagation of electromagnetic waves. However, the common formalism of coordinate transformations between any two inertial frames appears too ponderous to infer the existence of Minkowski space. For this reason, the time dilation and retardation, the contraction of the length along and the spatial invariance across the direction of relative motion of two frames are presented in a coordinate-free manner. This results in the transformation between two frames in the form of relationships between the time moments and the components of the position vector of a given event, along and across the directions of the frames' motion. The obtained transformation rules for the components of the position ve...

  8. Lebesgue Sets Immeasurable Existence

    Directory of Open Access Journals (Sweden)

    Diana Marginean Petrovai

    2012-12-01

    Full Text Available It is well known that the notion of measure and integral were released early enough in close connection with practical problems of measuring of geometric figures. Notion of measure was outlined in the early 20th century through H. Lebesgue’s research, founder of the modern theory of measure and integral. It was developed concurrently a technique of integration of functions. Gradually it was formed a specific area todaycalled the measure and integral theory. Essential contributions to building this theory was made by a large number of mathematicians: C. Carathodory, J. Radon, O. Nikodym, S. Bochner, J. Pettis, P. Halmos and many others. In the following we present several abstract sets, classes of sets. There exists the sets which are not Lebesgue measurable and the sets which are Lebesgue measurable but are not Borel measurable. Hence B ⊂ L ⊂ P(X.

  9. EXIST Perspective for SFXTs

    Science.gov (United States)

    Ubertini, Pietro; Sidoli, L.; Sguera, V.; Bazzano, A.

    2009-12-01

    Supergiant Fast X-ray Transients (SFXTs) are one of the most interesting (and unexpected) results of the INTEGRAL mission. They are a new class of HMXBs displaying short hard X-ray outbursts (duration less tha a day) characterized by fast flares (few hours timescale) and large dinamic range (10E3-10E4). The physical mechanism driving their peculiar behaviour is still unclear and highly debated: some models involve the structure of the supergiant companion donor wind (likely clumpy, in a spherical or non spherical geometry) and the orbital properties (wide separation with eccentric or circular orbit), while others involve the properties of the neutron star compact object and invoke very low magnetic field values (B 1E14 G, magnetars). The picture is still highly unclear from the observational point of view as well: no cyclotron lines have been detected in the spectra, thus the strength of the neutron star magnetic field is unknown. Orbital periods have been measured in only 4 systems, spanning from 3.3 days to 165 days. Even the duty cycle seems to be quite different from source to source. The Energetic X-ray Imaging Survey Telescope (EXIST), with its hard X-ray all-sky survey and large improved limiting sensitivity, will allow us to get a clearer picture of SFXTs. A complete census of their number is essential to enlarge the sample. A long term and continuous as possible X-ray monitoring is crucial to -(1) obtain the duty cycle, -(2 )investigate their unknown orbital properties (separation, orbital period, eccentricity),- (3) to completely cover the whole outburst activity, (4)-to search for cyclotron lines in the high energy spectra. EXIST observations will provide crucial informations to test the different models and shed light on the peculiar behaviour of SFXTs.

  10. A review of existing studies reporting the negative effects of alcohol access and positive effects of alcohol control policies on interpersonal violence

    Directory of Open Access Journals (Sweden)

    Jessica Laura Fitterer

    2015-11-01

    Full Text Available Alcohol consumption often leads to elevated rates of violence yet alcohol access policies continue to relax across the globe. Our review establishes the extent alcohol policy can moderate violent crime through alcohol availability restrictions. Results were informed from comprehensive selection of peer-reviewed journals from 1950 to October 2015. Our search identified 88 relevant studies on alcohol access and violence conducted across 12 countries. Seventeen studies included quasi-control design, and 23 conducted intervention analysis. Seventy-two (82% reported a significant relationship between alcohol access and violent offences. Alcohol outlet studies reported the greatest percentage of significant results (93%, with trading hours (63%, and alcohol price following (58%. Results from baseline studies indicated the effectiveness of increasing the price of commonly consumed alcohol, restricting the hours of alcohol trading, and limiting the number of alcohol outlets per region to prevent violent offences. Unclear are the effects of tax reductions, restriction of on-premises re-entry, and different outlet types on violent crime. Further, the generalization of statistics over broad areas and the low number of control/intervention studies poses some concern for confounding or correlated effects on study results, and amount of information for local level prevention of interpersonal violence. Future studies should focus on gathering longitudinal data, validating models, limiting crime data to peak drinking days and times, and wherever possible collecting the joint distribution between violent crime, intoxication, and place. A greater up take of local level analysis will benefit studies comparing the influence of multiple alcohol establishment types by relating the location of a crime to establishment proximity. Despite, some uncertainties particular studies showed that even modest policy changes such as 1% increases in alcohol price, one hour changes

  11. Does Congenital Heart Disease Affect Neurodevelopmental Outcomes in Children with Down Syndrome?

    Science.gov (United States)

    Alsaied, Tarek; Marino, Bradley S; Esbensen, Anna J; Anixt, Julia S; Epstein, Jeffery N; Cnota, James F

    2016-01-01

    The impact that congenital heart disease (CHD) has on the neurodevelopment of children with Down syndrome (DS) is unknown and potentially has implications for targeted early intervention. This study assessed the relationship between CHD that required surgery in the first year of life and neurodevelopmental, behavioral and emotional functioning outcomes in children with DS. A retrospective chart review of 1092 children (0-18 years) with DS who visited a single institution from 8/08-8/13 was performed. Children who underwent at least one of nine neurodevelopmental (cognitive, language, developmental) or academic tests were included in the analysis (N = 178). Cohort was age-divided into infants/toddlers (0-2 years), preschoolers (3-5 years), and school age/adolescent (6-18 years). Test scores of children with DS who underwent cardiac surgery in the first year of life were compared to children with DS without CHD. T test, chi-square and Mann Whitney U tests were used where appropriate. Infants/toddlers with cardiac surgery had lower scores for receptive (P = .01), expressive (P = .021) and composite language (P children with cardiac surgery there were no differences in IQ scores, language scores, or academic achievement scores compared to those without CHD. Also at school-age there was no difference in the incidence of ADHD, executive function or on internalizing and externalizing behavior scores. Children with DS undergoing cardiac surgery during the first year demonstrated poorer neurodevelopmental outcomes as infants/toddler but had no difference at school age compared to children with DS without CHD. These results will guide early interventions to optimize neurodevelopmental outcomes in children with DS and will help with family counseling after CHD repair. © 2016 Wiley Periodicals, Inc.

  12. Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement

    OpenAIRE

    Hori, Ikumi; Otomo, Takanobu; Nakashima, Mitsuko; Miya, Fuyuki; Negishi, Yutaka; SHIRAISHI, HIDEAKI; Nonoda, Yutaka; Magara, Shinichi; Tohyama, Jun; Okamoto, Nobuhiko; KUMAGAI, Takeshi; Shimoda, Konomi; Yukitake, Yoshiya; Kajikawa, Daigo; Morio, Tomohiro

    2017-01-01

    Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Mutations in EPG5, a gene that encodes a key autophagy regulator, have been shown to cause VICIS, however, the precise pathomechanism underlying VICIS is yet to be clarified. Here, we describe detailed clinical (including brain MRI and musc...

  13. EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

    OpenAIRE

    Byrne, Susan; Jansen, Lara; U-King-Im, Jean-Marie; Siddiqui, Ata; Lidov, Hart G. W.; Bodi, Istvan; Smith, Luke; Mein, Rachael; Cullup, Thomas; Dionisi-Vici, Carlo; Al-Gazali, Lihadh; Al-Owain, Mohammed; Bruwer, Zandre; Al Thihli, Khalid; El-Garhy, Rana

    2016-01-01

    Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations...

  14. Identification of neurodevelopmental disabilities in underserved children using telehealth (INvesT): Clinical trial study design.

    Science.gov (United States)

    Ciccia, Angela Hein; Roizen, Nancy; Garvey, Matt; Bielefeld, Roger; Short, Elizabeth J

    2015-11-01

    Children living in poverty are at high risk for delays in development of language and behavior and they experience a discrepancy in diagnosis and access to intervention services. This gap is partially caused by barriers in access as well as traits that are specific to each child and family. The Identification of Neurodevelopmental Disabilities in Underserved Children using Telehealth (INvesT) trial is a novel intervention approach that was specifically designed to address these barriers. The INvesT trial has three primary aims: 1) to reduce the age of identification of neurodevelopmental disability for high-risk, low-income children. 2) To validate the INvesT protocol as a service delivery model that will decrease age of identifications of neurodevelopmental disability for high-risk, low-income children; and 3) to identify important child-specific factors, family-specific factors, and environmental factors that impact feasibility and success of the INvesT trial for high-risk, low-income children. The INvesT trial is an open-label, double-blinded, placebo-controlled multi-level study that includes telehealth risk assessment, telehealth screening, traditional full assessment, and follow through to enrollment in early intervention. The trial is conducted in partnership with an urban community health clinic that largely serves a low-income patient population. The results of the INvesT trial will provide evidence for the use of a telehealth service delivery model to improve access to care for neurodevelopmental disabilities for high-risk, low-income children. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Rapamycin Prevents Seizures After Depletion of STRADA in a Rare Neurodevelopmental Disorder

    OpenAIRE

    Parker, Whitney E.; Orlova, Ksenia A.; Parker, William H.; Birnbaum, Jacqueline F.; Krymskaya, Vera P.; Goncharov, Dmitry A.; Baybis, Marianna; Helfferich, Jelte; Okochi, Kei; Strauss, Kevin A.; Crino, Peter B.

    2013-01-01

    A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase...

  16. Validation and adaptation of rapid neurodevelopmental assessment instrument for infants in Guatemala.

    Science.gov (United States)

    Thompson, L; Peñaloza, R A; Stormfields, K; Kooistra, R; Valencia-Moscoso, G; Muslima, H; Khan, N Z

    2015-11-01

    Timely detection of neurodevelopmental impairments in children can prompt referral for critical services that may prevent permanent disability. However, screening of impairments is a significant challenge in low-resource countries. We adapted and validated the rapid neurodevelopmental assessment (RNDA) instrument developed in Bangladesh to assess impairment in nine domains: primitive reflexes, gross and fine motor development, vision, hearing, speech, cognition, behaviour and seizures. We conducted a cross-sectional study of 77 infants (0-12 months) in rural Guatemala in July 2012 and July 2013. We assessed inter-rater reliability and predictive validity between the 27-item RNDA and the 325-item Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and concurrent validity based on chronic malnutrition, a condition associated with neurodevelopmental impairments. For both RNDA and BSID-III, standardized scores below 80 were defined as borderline impairment. Children came from rural households (92%), were born to indigenous women of Mayan descent (73%) and had moderate or severe growth stunting (43%). Inter-rater reliability for eight RNDA domains was of moderate to high reliability (weighted κ coefficients, 0.49-0.99). Children screened positive for impairment in fine motor (17%) and gross motor (14%) domains using the RNDA. The RNDA had good concurrent ability; infants who were growth stunted had higher mean levels of impairment in gross motor, speech and cognition domains (all p < 0.001). The RNDA took 20-30 min to complete compared with 45-60 min for BSID-III. Wide-scale implementation of a simple, valid and reliable screening tool like the RNDA by community health workers would facilitate early screening and referral of infants at-risk for neurodevelopmental impairment. © 2015 John Wiley & Sons Ltd.

  17. Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder? Evidence From a Four-Decade Longitudinal Cohort Study

    National Research Council Canada - National Science Library

    Moffitt, Terrie E; Houts, Renate; Asherson, Philip; Belsky, Daniel W; Corcoran, David L; Hammerle, Maggie; Harrington, HonaLee; Hogan, Sean; Meier, Madeline H; Polanczyk, Guilherme V; Poulton, Richie; Ramrakha, Sandhya; Sugden, Karen; Williams, Benjamin; Rohde, Luis Augusto; Caspi, Avshalom

    2015-01-01

    Objective:Despite a prevailing assumption that adult ADHD is a childhood-onset neurodevelopmental disorder, no prospective longitudinal study has described the childhoods of the adult ADHD population...

  18. Modulating Tone to Promote Motor Development Using a Neurofacilitation of Developmental Reaction (NFDR) Approach in Children with Neurodevelopmental Delay

    National Research Council Canada - National Science Library

    Vijay Batra; Meenakshi Batra; Ravindra Mohan Pandey; Vijai Prakash Sharma; Girdhar Gopal Agarwal

    2015-01-01

      [...]assessments of muscle tone and primitive reflex status are crucial parts of motor examinations and the formulation of intervention strategies for children with neurodevelopmental delay (3,4...

  19. Gateway Effects: Why the Cited Evidence Does Not Support Their Existence for Low-Risk Tobacco Products (and What Evidence Would).

    Science.gov (United States)

    Phillips, Carl V

    2015-05-21

    It is often claimed that low-risk drugs still create harm because of "gateway effects", in which they cause the use of a high-risk alternative. Such claims are popular among opponents of tobacco harm reduction, claiming that low-risk tobacco products (e.g., e-cigarettes, smokeless tobacco) cause people to start smoking, sometimes backed by empirical studies that ostensibly support the claim. However, these studies consistently ignore the obvious alternative causal pathways, particularly that observed associations might represent causation in the opposite direction (smoking causes people to seek low-risk alternatives) or confounding (the same individual characteristics increase the chance of using any tobacco product). Due to these complications, any useful analysis must deal with simultaneity and confounding by common cause. In practice, existing analyses seem almost as if they were designed to provide teaching examples about drawing simplistic and unsupported causal conclusions from observed associations. The present analysis examines what evidence and research strategies would be needed to empirically detect such a gateway effect, if there were one, explaining key methodological concepts including causation and confounding, examining the logic of the claim, identifying potentially useful data, and debunking common fallacies on both sides of the argument, as well as presenting an extended example of proper empirical testing. The analysis demonstrates that none of the empirical studies to date that are purported to show a gateway effect from tobacco harm reduction products actually does so. The observations and approaches can be generalized to other cases where observed association of individual characteristics in cross-sectional data could result from any of several causal relationships.

  20. Utilization of the Premature Birth Knowledge Scale to Assess Pediatric Provider Knowledge of Neurodevelopmental Outcomes.

    Science.gov (United States)

    Kelly, Michelle M; Dean, Spencer

    Prematurity affects a significant portion (10-12%) of children in the Unites States, with potential for physical, psychological, neurodevelopmental, and behavioral impairments continuing long past the neonatal period. The specific aim of this research was to evaluate pediatric primary and specialty care providers' knowledge and understanding of neurodevelopmental outcomes of children born prematurely. Pediatric nurse practitioner (PNP) members of the National Association of Pediatric Nurse Practitioners participated in an online survey using the 33-item Premature Birth Knowledge Scale (PB-KS) to assess their knowledge of current neurodevelopmental outcomes of children born prematurely. Neither years of practice as a registered nurse nor as a PNP predicted performance on the PB-KS. The mean score on the PB-KS in the PNP sample was 17.8 (possible score = 0-33), with a mean accuracy of 53.9%. Higher scores on the PB-KS were correlated with higher perceived level of preparation to care for children born prematurely. To our knowledge, this is the first study to use the PB-KS with pediatric primary and specialty providers. PNPs are uniquely situated to educate and support families facing the long-term consequences of premature birth; to do so they must maintain accurate understanding of current outcomes. Copyright © 2017 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  1. Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology.

    LENUS (Irish Health Repository)

    2011-01-01

    Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.

  2. Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming

    Directory of Open Access Journals (Sweden)

    Mark Wade

    2015-01-01

    Full Text Available Neurodevelopmental disorders represent a broad class of childhood neurological conditions that have a significant bearing on the wellbeing of children, families, and communities. In this review, we draw on evidence from two common and widely studied neurodevelopmental disorders—autism spectrum disorder (ASD and attention-deficit hyperactivity disorder (ADHD—to demonstrate the utility of genetically informed sibling designs in uncovering the nature and pathogenesis of these conditions. Specifically, we examine how twin, recurrence risk, and infant prospective tracking studies have contributed to our understanding of genetic and environmental liabilities towards neurodevelopmental morbidity through their impact on neurocognitive processes and structural/functional neuroanatomy. It is suggested that the siblings of children with ASD and ADHD are at risk not only of clinically elevated problems in these areas, but also of subthreshold symptoms and/or subtle impairments in various neurocognitive skills and other domains of psychosocial health. Finally, we close with a discussion on the practical relevance of sibling designs and how these might be used in the service of early screening, prevention, and intervention efforts that aim to alleviate the negative downstream consequences associated with disorders of neurodevelopment.

  3. An interdisciplinary bronchopulmonary dysplasia program is associated with improved neurodevelopmental outcomes and fewer rehospitalizations.

    Science.gov (United States)

    Shepherd, E G; Knupp, A M; Welty, S E; Susey, K M; Gardner, W P; Gest, A L

    2012-01-01

    Bronchopulmonary dysplasia (BPD) is a pulmonary disease associated with poor neurodevelopmental and medical outcomes. Patients with BPD are medically fragile, at high risk for complications and require interdisciplinary care. We tested the hypothesis that a chronic care approach for BPD would improve neurodevelopmental outcomes relative to the National Institute of Child and Human Development Neonatal Research Network (NICHD NRN) and reduce medical complications. Infants were followed as inpatients and outpatients. Bayley developmental exams were carried out at 18-24 months of age and compared with the NICHD NRN report. Finally, rates of readmission (a proxy for medical complications) were compared before and after implementation of the Comprehensive Center for BPD (CCBPD). Developmental scores obtained in 2007 and 2008 show that 12 and 10% of patients with moderate BPD (n=61) had Bayley Scores <70 for mental and motor indices respectively, whereas corresponding national rates were 35 and 26%. For patients with severe BPD (n=46), 15 and 11% of patients within the CCBPD vs 50 and 42% of national patients scored <70 for mental and motor indices, respectively. Finally, readmission rates dropped from 29% in the year before the implementation of the CCPD (n=269) to 5% thereafter (n=866, P<0.0001). The encouraging neurodevelopmental outcomes and readmission rates associated with a chronic care approach to BPD suggest these infants may be best served by a comprehensive interdisciplinary approach to care that focuses on neurodevelopment throughout the hospital stay.

  4. Increased risk of neuropsychological disorders in children born preterm without major disabilities: a neurodevelopmental model

    Directory of Open Access Journals (Sweden)

    Dipasquale Filippo

    2009-06-01

    Full Text Available Over the past 30 years, preterm births have drastically increased and today represent 12.5% of total births. About 1.2% of preterm births characterize very preterm births (GA<32weeks that, with very low birth weight (BW<1500grams, are constantly found as risk factors of unfavourable neurological outcomes in longitudinal follow up studies. Actually, also “late preterm” children (preterm born from 33 to 36 weeks of gestational age, normally considered at low risk for neurodevelopmental disabilities, are supposed to represent a population of children to be monitored. Previous findings of a general cognitive impairment in children born preterm have gradually addressed the assessment of more specific neuropsychological skills and pointed out the importance to follow these children up to adolescent age. The neuroanatomical prerequisite of an abnormality in frontal lobe development and the correlation with various neuropsychological dysfunctions (fine and gross motor disabilities, executive function and working memory deficits, visual-constructional and attentional dysfunctions underline the interference of preterm birth with normal brain maturational phases. Though showing more demanding neurodevelopmental pathways than term peers, a large number of preterm children tend to functionally normalize in adolescence. The review supports the hypothesis of a neurodevelopmental model that can be at risk to influence dysfunctional neuropsychological outcome.

  5. Early Life Characteristics and Neurodevelopmental Phenotypes in the Mount Sinai Children's Environmental Health Center.

    Science.gov (United States)

    Furlong, Melissa; Herring, Amy H; Goldman, Barbara D; Daniels, Julie L; Wolff, Mary S; Engel, Lawrence S; Engel, Stephanie M

    2017-11-24

    Neurodevelopmental outcomes including behavior, executive functioning, and IQ exhibit complex correlational structures, although they are often treated as independent in etiologic studies. We performed a principal components analysis of the behavioral assessment system for children, the behavior rating inventory of executive functioning, and the Wechsler scales of intelligence in a prospective birth cohort, and estimated associations with early life characteristics. We identified seven factors: (1) impulsivity and externalizing, (2) executive functioning, (3) internalizing, (4) perceptual reasoning, (5) adaptability, (6) processing speed, and (7) verbal intelligence. Prenatal fish consumption, maternal education, preterm birth, and the home environment were important predictors of various neurodevelopmental factors. Although maternal smoking was associated with more adverse externalizing, executive functioning, and adaptive composite scores in our sample, of the orthogonally-rotated factors, smoking was only associated with the impulsivity and externalizing factor ([Formula: see text] - 0.82, 95% CI - 1.42, - 0.23). These differences may be due to correlations among outcomes that were accounted for by using a phenotypic approach. Dimension reduction may improve upon traditional approaches by accounting for correlations among neurodevelopmental traits.

  6. Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study.

    Science.gov (United States)

    Kerekes, Nóra; Lundström, Sebastian; Chang, Zheng; Tajnia, Armin; Jern, Patrick; Lichtenstein, Paul; Nilsson, Thomas; Anckarsäter, Henrik

    2014-01-01

    Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD) and conduct disorder (CD). The aims of this study were to identify gender-specific associations between the behavioural problems-ODD/CD-like problems-and the neurodevelopmental disorders-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD)-and to investigate underlying genetic effects. Methods. 17,220 twins aged 9 or 12 were screened using the Autism-Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting. Results. Social interaction problems (one of the ASD subdomains) was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%-62% of the variance in behavioural problems, except in CD-like problems in girls (26%). Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls. Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.

  7. Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study

    Directory of Open Access Journals (Sweden)

    Nóra Kerekes

    2014-04-01

    Full Text Available Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD and conduct disorder (CD. The aims of this study were to identify gender-specific associations between the behavioural problems–ODD/CD-like problems–and the neurodevelopmental disorders–attention deficit hyperactivity disorder (ADHD, autism spectrum disorder (ASD–and to investigate underlying genetic effects.Methods. 17,220 twins aged 9 or 12 were screened using the Autism–Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting.Results. Social interaction problems (one of the ASD subdomains was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%–62% of the variance in behavioural problems, except in CD-like problems in girls (26%. Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls.Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.

  8. The effects of aerobic exercise for persons with migraine and co-existing tension-type headache and neck pain. A randomized, controlled, clinical trial

    DEFF Research Database (Denmark)

    Krøll, Lotte Skytte; Hammarlund, Catharina Sjödahl; Linde, Mattias

    2018-01-01

    Aim To evaluate aerobic exercise in migraine and co-existing tension-type headache and neck pain. Methods Consecutively recruited persons with migraine and co-existing tension-type headache and neck pain were randomized into an exercise group or control group. Aerobic exercise consisted of bike/c...

  9. An investigation into the effects of different existing states of aluminum isopropoxide on copper-based catalysts for direct synthesis of dimethyl ether from syngas

    Science.gov (United States)

    Sun, Kai; Wang, Peng; Bian, Zhongkai; Huang, Wei

    2018-01-01

    Aluminum isopropoxide (AIP) is a vital raw material to produce high surface area alumina catalyst, which is used for catalytic applications, such as hydrocracking, Fischer-Tropsch and STD (syngas to dimethyl ether) reactions. However, the different existing states have an effect on hydrolysis and condensation in the process of precursor preparation. The Cu/Zn/Al slurry catalysts were prepared by aluminum isopropoxide, which were liquid state, crystalline state and solid state, utilizing a complete liquid phase preparation technology. In the dimethyl ether (DME) synthesis reaction, the aluminum resource of crystalline state was prepared for slurry catalyst, which presented high CO conversion and DME selectivity of 54.32% and 69.74%, respectively. Characterization results indicated that different forms of AIP have the variant coordination numbers of Al-O and polymerization degrees, and the catalyst prepared by crystalline state consists amount of tetra-coordinated Al and few hexa-coordinated Al, which can exert different hydrolysis and condensation process compared with other aluminum sources, and finally it contributes to the strong interaction between active site copper species and Zn/Al species, confirming more Cu+ is responsible for the synthesis of DME in the slurry reactor.

  10. Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study.

    Science.gov (United States)

    Lindenburg, Irene T; Smits-Wintjens, Vivianne E; van Klink, Jeanine M; Verduin, Esther; van Kamp, Inge L; Walther, Frans J; Schonewille, Henk; Doxiadis, Ilias I; Kanhai, Humphrey H; van Lith, Jan M; van Zwet, Erik W; Oepkes, Dick; Brand, Anneke; Lopriore, Enrico

    2012-02-01

    To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT). Neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of Intelligence, and the Wechsler Intelligence Scale for Children, according to the children's age. Primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness. A total of 291 children were evaluated at a median age of 8.2 years (range, 2-17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis including only preoperative risk factors, severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7-92.7). Incidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome. Copyright © 2012 Mosby, Inc. All rights reserved.

  11. Effectiveness of telemonitoring integrated into existing clinical services on hospital admission for exacerbation of chronic obstructive pulmonary disease: researcher blind, multicentre, randomised controlled trial.

    Science.gov (United States)

    Pinnock, Hilary; Hanley, Janet; McCloughan, Lucy; Todd, Allison; Krishan, Ashma; Lewis, Stephanie; Stoddart, Andrew; van der Pol, Marjon; MacNee, William; Sheikh, Aziz; Pagliari, Claudia; McKinstry, Brian

    2013-10-17

    To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care. Researcher blind, multicentre, randomised controlled trial. UK primary care (Lothian, Scotland). Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation. We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems. Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring. Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments. Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds. Both groups received similar care from existing clinical services. The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation. Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George's respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment. Analysis was intention to treat. Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar. The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44). Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59). Mean duration of COPD admissions over

  12. Gateway Effects: Why the Cited Evidence Does Not Support Their Existence for Low-Risk Tobacco Products (and What Evidence Would

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    Carl V. Phillips

    2015-05-01

    Full Text Available It is often claimed that low-risk drugs still create harm because of “gateway effects”, in which they cause the use of a high-risk alternative. Such claims are popular among opponents of tobacco harm reduction, claiming that low-risk tobacco products (e.g., e-cigarettes, smokeless tobacco cause people to start smoking, sometimes backed by empirical studies that ostensibly support the claim. However, these studies consistently ignore the obvious alternative causal pathways, particularly that observed associations might represent causation in the opposite direction (smoking causes people to seek low-risk alternatives or confounding (the same individual characteristics increase the chance of using any tobacco product. Due to these complications, any useful analysis must deal with simultaneity and confounding by common cause. In practice, existing analyses seem almost as if they were designed to provide teaching examples about drawing simplistic and unsupported causal conclusions from observed associations. The present analysis examines what evidence and research strategies would be needed to empirically detect such a gateway effect, if there were one, explaining key methodological concepts including causation and confounding, examining the logic of the claim, identifying potentially useful data, and debunking common fallacies on both sides of the argument, as well as presenting an extended example of proper empirical testing. The analysis demonstrates that none of the empirical studies to date that are purported to show a gateway effect from tobacco harm reduction products actually does so. The observations and approaches can be generalized to other cases where observed association of individual characteristics in cross-sectional data could result from any of several causal relationships.

  13. [Neurodevelopmental disorders in response to hormonally active environmental pollutants].

    Science.gov (United States)

    Kajta, Małgorzata; Wójtowicz, Anna

    2010-01-01

    In recent years, the major concern has been focused on persistent organic pollutants (POPs), which are present in ecosphere in increasing concentrations, especially since 1950s. Among of these pollutants are dioxins and polychlorinated biphenyls (PCBs) released during vast burning and plastics processing, as well as pesticides which were industrial chemicals intensively produced for many years. In last decade, dioxins together with PCBs and pesticides have been classified as endocrine disrupting chemicals, because they are able to alter hormone-dependent processes and disrupt functioning of endocrine glands, e.g. thyroid and gonads. Furthermore, these pollutants have been included in neural disrupting chemicals due to their ability of altering neural transmission and formation of neural networks. Since POPs may persist in the environment for dozens of years, an exposure to these organic pollutants creates a serious issue for environmental toxicologists. POP intoxication creates severe clinical problems, which became evident in dramatic circumstances, e.g. Yusho incident in Japan, Yu-Cheng incident in Tajwan, Michigan Lake poisoning. Clinical problems have been recognized as disruption of thyroid and gonadal functions, immunodeficiency as well as psychomotor deficits and increased occurrence of hormone-dependent cancers. Thus, knowledge on POP effects on human nervous system has been related mainly to toxic effects of these organic pollutants. Little is known, however, about the action of very low, so called background, doses of POPs and their effects on hormonal homeostasis in developing brain. It is of particular importance, because doses which are low for adults might become toxic for fetuses, infants or children. Recently, the public concern has been focused on POP effects on brain function, concomitantly with the increase in neuropsychiatric disorders, including autism, attention deficit and hyperactivity disorder (ADHD) as well as learning disabilities

  14. Effects of adding a new PCMH block rotation and resident team to existing longitudinal training within a certified PCMH: primary care residents’ attitudes, knowledge, and experience

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    Anandarajah G

    2016-08-01

    Full Text Available Gowri Anandarajah,1,2 Christopher Furey,1 Rabin Chandran,1 Arnold Goldberg,3,4 Fadya El Rayess,1 David Ashley,1 Roberta E Goldman,1,5 1Department of Family Medicine, 2Department of Medical Science, Warren Alpert Medical School of Brown University, Providence, RI, 3Department of Family Medicine, University of South Florida Morsani College of Medicine, Tampa, FL, 4Department of Family Medicine, Leigh Valley Family Health Network, Allentown, PA, 5Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA Background: Although the patient-centered medical home (PCMH model is considered important for the future of primary care in the USA, it remains unclear how best to prepare trainees for PCMH practice and leadership. Following a baseline study, the authors added a new required PCMH block rotation and resident team to an existing longitudinal PCMH immersion and didactic curriculum within a Level 3-certified PCMH, aiming for “enhanced situated learning”. All 39 residents enrolled in a USA family medicine residency program during the first year of curricular implementation completed this new 4-week rotation. This study examines the effects of this rotation after 1 year. Methods: A total of 39 intervention and 13 comparison residents were eligible participants. This multimethod study included: 1 individual interviews of postgraduate year (PGY 3 intervention vs PGY3 comparison residents, assessing residents’ PCMH attitudes, knowledge, and clinical experience, and 2 routine rotation evaluations. Interviews were audiorecorded, transcribed, and analyzed using immersion/crystallization. Rotation evaluations were analyzed using descriptive statistics and qualitative analysis of free text responses. Results: Authors analyzed 23 interviews (88% and 26 rotation evaluations (67%. Intervention PGY3s’ interviews revealed more nuanced understanding of PCMH concepts and more experience with system-level PCMH

  15. Towards a Neurodevelopmental Model of Clinical Case Formulation

    OpenAIRE

    Solomon, Marjorie; Hessl, David; Chiu, Sufen; Olsen, Emily; Hendren, Robert

    2009-01-01

    Rapid advances in molecular genetics and neuroimaging over the last 10-20 years have been a catalyst for research in neurobiology, developmental psychopathology, and translational neuroscience. Methods of study in psychiatry, previously described as “slow maturing,” now are becoming sufficiently sophisticated to more effectively investigate the biology of higher mental processes. Despite these technological advances, the recognition that psychiatric disorders are disorders of neurodevelopment...

  16. Cytokines and the neurodevelopmental basis of mental illness

    Directory of Open Access Journals (Sweden)

    Udani eRatnayake

    2013-10-01

    Full Text Available Epidemiological studies suggest that prenatal exposure to different types of viral or bacterial infections may be associated with similar outcomes; i.e., an increased risk of mental illness disorders in the offspring. Infections arising from various causes have similar debilitating effects in later life, suggesting that the exact pathogen may not be the critical factor in determining the neurological and cognitive outcome in the offspring. Instead, it is thought that response of the innate immune system, specifically the increased production of inflammatory cytokines, may be the critical mediator in altering fetal brain development pre-disposing the offspring to mental illness disorders later in life. Inflammatory cytokines are essential for normal brain development. Factors such as the site of cytokine production, a change in balance between anti- and pro- inflammatory cytokines, placental transfer of cytokines, the effects of cytokines on glial cells, and the effects of glucocorticoids are important when evaluating the impact of maternal infection on fetal brain development. Although it is clear that cytokines are altered in the fetal brain following maternal infection, further evidence is required to determine if cytokines are the critical factor that alters the trajectory of brain development, subsequently leading to postnatal behavioural and neurological abnormalities.

  17. Prognostic effects of rosuvastatin in patients with co-existing chronic obstructive pulmonary disease and chronic heart failure: A sub-analysis of GISSI-HF trial.

    Science.gov (United States)

    Rossi, Andrea; Inciardi, Riccardo M; Rossi, Andrea; Temporelli, Pier Luigi; Lucci, Donata; Gonzini, Lucio; Marchioli, Roberto; Nicolosi, Gian Luigi; Tavazzi, Luigi

    2017-06-01

    Rising evidences showed a possible protective role of statins in chronic obstructive pulmonary disease (COPD). We aimed to evaluate in a post-hoc analysis of the GISSI-HF trial the prognostic effect of the use of rosuvastatin in patients with co-existing COPD and HF, assuming that the anti-inflammatory properties of these drugs may imply a potential beneficial effect in these associated chronic inflammatory conditions. We analyzed patients with chronic HF and history of COPD deriving from the GISSI-HF study. Of all 4574 patients eligible to statin, 1060 ambulatory patients with HF and concomitant COPD were enrolled and randomly assigned to rosuvastatin 10 mg daily (538 patients) or placebo (522 patients). The primary end-point was to compare all cause death rate in patients randomized to rosuvastatin or placebo. Further, we assessed the effects of rosuvastatin (10 mg daily) on cardiovascular (CV) death, non-CV death and hospital admissions. Median follow-up was 3.9 years with an interquartile range (IQR) of 3.0-4.4. During the follow-up 438 (41.3%) patients died, 304 (28.6%) for CV death and 687 (64.8%) had at least one hospitalization. The two patient groups had similar outcome, irrespective of randomization, in terms of all-cause mortality (log-rank test p = 0.30) CV, non CV-death (p = 0.88 and 0.09 respectively) and all-cause hospitalization (p = 0.82). Cox regression analysis did not show a favorable association between the use of statin and the examined end-points both on unadjusted and adjusted models. Statin use is not associated with a beneficial effects on all cause, CV, non CV mortality and hospitalization in patients with coexistent chronic HF and history of COPD. ClinicalTrials.gov Identifier: NCT00336336. Copyright © 2017. Published by Elsevier Ltd.

  18. Mauriac syndrome still exists.

    Science.gov (United States)

    Dias, Joana; Martins, Sofia; Carvalho, Susana; Marques, Olinda; Antunes, Ana

    2013-05-01

    Mauriac syndrome (MS) is a rare complication of type 1 diabetes mellitus (DM1). It is related to low insulin concentrations and is less common since longer-acting insulins became available. It is characterized by hepatomegaly, growth and puberty delay, and the presence of elevated transaminases and serum lipids. The aim of this study was to describe the patients from a pediatric diabetic population that fulfill the criteria of MS. A retrospective analysis of the pediatric diabetic population with diagnostic criteria of MS currently followed at Hospital de Braga, was performed. From a population of 91 patients with DM1 18 years, 6 patients with the criteria for MS were identified: 5 girls, and 1 boy. The age at presentation was 13-17 years, with a minimum interval between DM1 diagnosis and MS criteria of 4 years. All the patients were prescribed intensive insulin therapy (median daily insulin dose: 0.88 U/kg). All had a previous history of poor glycemic control before the diagnosis of MS with glycated hemoglobin (HbA1c) between 8.8 and 12.9%. Increase of hepatic enzymes was present in all the patients; 4 of them had associated hepatomegaly. All the girls presented puberty delay and cushingoid features. None of the patients presented short stature and 5 of them presented mixed dyslipidemia. Although MS is an ancient entity described in DM1, it still exists, particularly in adolescent females. Being aware of MS is of extreme importance since most of the clinical features are reversible with better glycemic control. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  19. Why Does Leadership Exist?

    Science.gov (United States)

    Caulfield, Jay

    2013-01-01

    What style of leadership is most effective in a particular situation with a specific group of followers? How do leaders best motivate followers in achieving goals? Although important questions, before we may come to fully understand the "how" and "what" of leadership, in this brief I suggest that we reflect upon a more basic…

  20. Molecular and neurodevelopmental benefits to children of closure of a coal burning power plant in China.

    Directory of Open Access Journals (Sweden)

    Deliang Tang

    Full Text Available Polycyclic aromatic hydrocarbons (PAH are major toxic air pollutants released during incomplete combustion of coal. PAH emissions are especially problematic in China because of their reliance on coal-powered energy. The prenatal period is a window of susceptibility to neurotoxicants. To determine the health benefits of reducing air pollution related to coal-burning, we compared molecular biomarkers of exposure and preclinical effects in umbilical cord blood to neurodevelopmental outcomes from two successive birth cohorts enrolled before and after a highly polluting, coal-fired power plant in Tongliang County, China had ceased operation. Women and their newborns in the two successive cohorts were enrolled at the time of delivery. We measured PAH-DNA adducts, a biomarker of PAH-exposure and DNA damage, and brain-derived neurotrophic factor (BDNF, a protein involved in neuronal growth, in umbilical cord blood. At age two, children were tested using the Gesell Developmental Schedules (GDS. The two cohorts were compared with respect to levels of both biomarkers in cord blood as well as developmental quotient (DQ scores across 5 domains. Lower levels of PAH-DNA adducts, higher concentrations of the mature BDNF protein (mBDNF and higher DQ scores were seen in the 2005 cohort enrolled after closure of the power plant. In the two cohorts combined, PAH-DNA adducts were inversely associated with mBDNF as well as scores for motor (p = 0.05, adaptive (p = 0.022, and average (p = 0.014 DQ. BDNF levels were positively associated with motor (p = 0.018, social (p = 0.001, and average (p = 0.017 DQ scores. The findings indicate that the closure of a coal-burning plant resulted in the reduction of PAH-DNA adducts in newborns and increased mBDNF levels that in turn, were positively associated with neurocognitive development. They provide further evidence of the direct benefits to children's health as a result of the coal plant shut down

  1. The use of MElatonin in children with neurodevelopmental disorders and impaired sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS).

    Science.gov (United States)

    Appleton, R E; Jones, A P; Gamble, C; Williamson, P R; Wiggs, L; Montgomery, P; Sutcliffe, A; Barker, C; Gringras, P

    2012-01-01

    Difficulties in initiating and maintaining sleep are common in children with neurodevelopmental disorders. Melatonin is unlicensed in children yet widely prescribed for sleep problems. To determine whether or not immediate-release melatonin is beneficial compared with placebo in improving total duration of night-time sleep in children with neurodevelopmental problems. Randomised, double-blind, placebo-controlled, parallel study. Hospitals throughout England and Wales recruited patients referred by community paediatricians and other clinical colleagues. Children with neurodevelopmental problems aged from 3 years to 15 years 8 months who did not fall asleep within 1 hour of lights out or who had children were screened to enter the trial; 263 (96%) children were registered and completed the 4- to 6-week behaviour therapy period and 146 (56%) children were randomised, of whom 110 (75%) contributed data for the primary outcome. The difference in TST time between the melatonin and placebo groups adjusted for baseline was 22.43 minutes [95% confidence interval (CI) 0.52 to 44.34 minutes; p = 0.04] measured using sleep diaries. A reduction in SOL, adjusted for baseline, was seen for melatonin compared with placebo when measured by sleep diaries (-37.49 minutes, 95% CI -55.27 to -19.71 minutes; p children treated with melatonin slept 23 minutes longer than those in the placebo group; however, the upper limit of the confidence interval was less than 1 hour, the minimum clinically worthwhile difference specified at the outset of the trial. Melatonin is effective in reducing SOL in children with neurodevelopmental delay by a mean of 45 minutes; a value of 30 minutes was specified a priori to be clinically important. Future studies should be conducted over longer periods and directly compare different formulations of melatonin with conventional hypnotic and sedative medications. It would also be important to study groups of children with specific neurological disorders. Current

  2. Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses.

    Science.gov (United States)

    Wasser, Catherine R; Herz, Joachim

    2017-01-27

    Over half a century ago, D. S. Falconer first reported a mouse with a reeling gate. Four decades later, the Reln gene was isolated and identified as the cause of the reeler phenotype. Initial studies found that loss of Reelin, a large, secreted glycoprotein encoded by the Reln gene, results in abnormal neuronal layering throughout several regions of the brain. In the years since, the known functions of Reelin signaling in the brain have expanded to include multiple postdevelopmental neuromodulatory roles, revealing an ever increasing body of evidence to suggest that Reelin signaling is a critical player in the modulation of synaptic function. In writing this review, we intend to highlight the most fundamental aspects of Reelin signaling and integrate how these various neuromodulatory effects shape and protect synapses. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Postnatal brain development: Structural imaging of dynamic neurodevelopmental processes

    Science.gov (United States)

    Jernigan, Terry L.; Baaré, William F. C.; Stiles, Joan; Madsen, Kathrine Skak

    2013-01-01

    After birth, there is striking biological and functional development of the brain’s fiber tracts as well as remodeling of cortical and subcortical structures. Behavioral development in children involves a complex and dynamic set of genetically guided processes by which neural structures interact constantly with the environment. This is a protracted process, beginning in the third week of gestation and continuing into early adulthood. Reviewed here are studies using structural imaging techniques, with a special focus on diffusion weighted imaging, describing age-related brain maturational changes in children and adolescents, as well as studies that link these changes to behavioral differences. Finally, we discuss evidence for effects on the brain of several factors that may play a role in mediating these brain–behavior associations in children, including genetic variation, behavioral interventions, and hormonal variation associated with puberty. At present longitudinal studies are few, and we do not yet know how variability in individual trajectories of biological development in specific neural systems map onto similar variability in behavioral trajectories. PMID:21489384

  4. Neurodevelopmental and psychiatric issues in Down's syndrome: assessment and intervention.

    Science.gov (United States)

    Vicari, Stefano; Pontillo, Maria; Armando, Marco

    2013-06-01

    Down's syndrome (DS) is the most frequent genetic cause of intellectual disability and patients with DS show significant psychopathology (18-23%). Moreover, individuals with DS often show a cognitive decline associated with ageing characterized by a deterioration in memory, language and cognitive functioning. According to these relevant findings, an overview is presented of state-of-the-art knowledge of the neurocognitive, neurobiological and psychopathological profile, assessment and treatment of patients with DS. The linguistic characteristics of DS develop differently along distinct developmental trajectories. Thus, for example, morphosyntax deficit, especially in production, is more evident in adolescence than in early childhood and lexicon is usually better preserved in all ages (at least in comprehension). So far, rehabilitation is the only effective approach for improving cognitive and linguistic abilities. However, ongoing preliminary reports on other approaches such as transmagnetic stimulation or drugs suggest alternative or integrative treatment for the future. Individuals with DS show typical organization of brain structures related to some cognitive abilities, such as reduced volume in frontal and prefrontal areas, which is related to poor executive and linguistic abilities. They also frequently show psychiatric disorders such as externalizing disorders as well as depression, anxiety and obsessive-compulsive disorder. Nevertheless, as for other genetic syndrome with intellectual disability, there is a significant lack of research specifically focused on treatments of psychiatric and behavioural problems in DS. This is true both for psychosocial and for pharmacological interventions.

  5. The Peaceful Co-existence of Input Frequency and Structural Intervention Effects on the Comprehension of Complex Sentences in German-Speaking Children

    Directory of Open Access Journals (Sweden)

    Flavia Adani

    2017-09-01

    Full Text Available The predictions of two contrasting approaches to the acquisition of transitive relative clauses were tested within the same groups of German-speaking participants aged from 3 to 5 years old. The input frequency approach predicts that object relative clauses with inanimate heads (e.g., the pullover that the man is scratching are comprehended earlier and more accurately than those with an animate head (e.g., the man that the boy is scratching. In contrast, the structural intervention approach predicts that object relative clauses with two full NP arguments mismatching in number (e.g., the man that the boys are scratching are comprehended earlier and more accurately than those with number-matching NPs (e.g., the man that the boy is scratching. These approaches were tested in two steps. First, we ran a corpus analysis to ensure that object relative clauses with number-mismatching NPs are not more frequent than object relative clauses with number-matching NPs in child directed speech. Next, the comprehension of these structures was tested experimentally in 3-, 4-, and 5-year-olds respectively by means of a color naming task. By comparing the predictions of the two approaches within the same participant groups, we were able to uncover that the effects predicted by the input frequency and by the structural intervention approaches co-exist and that they both influence the performance of children on transitive relative clauses, but in a manner that is modulated by age. These results reveal a sensitivity to animacy mismatch already being demonstrated by 3-year-olds and show that animacy is initially deployed more reliably than number to interpret relative clauses correctly. In all age groups, the animacy mismatch appears to explain the performance of children, thus, showing that the comprehension of frequent object relative clauses is enhanced compared to the other conditions. Starting with 4-year-olds but especially in 5-year-olds, the number mismatch

  6. The Peaceful Co-existence of Input Frequency and Structural Intervention Effects on the Comprehension of Complex Sentences in German-Speaking Children.

    Science.gov (United States)

    Adani, Flavia; Stegenwallner-Schütz, Maja; Niesel, Talea

    2017-01-01

    The predictions of two contrasting approaches to the acquisition of transitive relative clauses were tested within the same groups of German-speaking participants aged from 3 to 5 years old. The input frequency approach predicts that object relative clauses with inanimate heads (e.g., the pullover that the man is scratching) are comprehended earlier and more accurately than those with an animate head (e.g., the man that the boy is scratching). In contrast, the structural intervention approach predicts that object relative clauses with two full NP arguments mismatching in number (e.g., the man that the boys are scratching) are comprehended earlier and more accurately than those with number-matching NPs (e.g., the man that the boy is scratching). These approaches were tested in two steps. First, we ran a corpus analysis to ensure that object relative clauses with number-mismatching NPs are not more frequent than object relative clauses with number-matching NPs in child directed speech. Next, the comprehension of these structures was tested experimentally in 3-, 4-, and 5-year-olds respectively by means of a color naming task. By comparing the predictions of the two approaches within the same participant groups, we were able to uncover that the effects predicted by the input frequency and by the structural intervention approaches co-exist and that they both influence the performance of children on transitive relative clauses, but in a manner that is modulated by age. These results reveal a sensitivity to animacy mismatch already being demonstrated by 3-year-olds and show that animacy is initially deployed more reliably than number to interpret relative clauses correctly. In all age groups, the animacy mismatch appears to explain the performance of children, thus, showing that the comprehension of frequent object relative clauses is enhanced compared to the other conditions. Starting with 4-year-olds but especially in 5-year-olds, the number mismatch supported

  7. IIAM (important information about me): a patient portability profile app for adults, children and families with neurodevelopmental disabilities.

    Science.gov (United States)

    Jiam, N T; Hoon, A H; Hostetter, C F; Khare, M M

    2017-08-01

    To describe the development of important information about me (IIAM), an application (app) used to communicate and organize healthcare information for people with neurodevelopmental disabilities (NDD). Prior to the development of IIAM version 1.0, households with NDD were selected to participate in a focus group. Respondents (n = 7) were parents of children with NDD. Participants were asked to use a beta version for at least 2 months in day-to-day applications and to complete a questionnaire at the end of the trial. Over half (57%) of the participants found the beta version to be useful. The greatest limitation in usability was the child's age and literacy level. All participants found the app to be visually appealing and easy to navigate. IIAM was commonly used to communicate information to caregivers, and to facilitate quality interactions between the child and others. Mobile technology has become ubiquitous and has emerged as an important tool in healthcare. New applications could potentially promote accessible, cost-effective and self-managed interventions for the disability community. IIAM is a user-friendly, well-accepted and useful app for people with NDD. The focus group feedback elicited from the beta testing was used to develop the IIAM app version 1.0. However, the sample size in this initial feasibility study is small, and warrants a prospective study that evaluates the overall benefits of this app in improving quality of life and helping individuals with developmental disabilities manage their day-to-day activities. Implications for Rehabilitation Mobile technology has been more ubiquitous in health care and has emerged as a tool in communicating healthcare needs. New applications could potentially promote accessible, cost-effective and self-managed interventions for the disability community. IIAM (important information about me) is a new iOS application that enables adults and children with neurodevelopmental disabilities to organize their medical

  8. Do `negative' temperatures exist?

    Science.gov (United States)

    Lavenda, B. H.

    1999-06-01

    A modification of the second law is required for a system with a bounded density of states and not the introduction of a `negative' temperature scale. The ascending and descending branches of the entropy versus energy curve describe particle and hole states, having thermal equations of state that are given by the Fermi and logistic distributions, respectively. Conservation of energy requires isentropic states to be isothermal. The effect of adiabatically reversing the field is entirely mechanical because the only difference between the two states is their energies. The laws of large and small numbers, leading to the normal and Poisson approximations, characterize statistically the states of infinite and zero temperatures, respectively. Since the heat capacity also vanishes in the state of maximum disorder, the third law can be generalized in systems with a bounded density of states: the entropy tends to a constant as the temperature tends to either zero or infinity.

  9. Turing Revisited: Decoding the microRNA Messages in Brain Extracellular Vesicles for Early Detection of Neurodevelopmental Disorders.

    Science.gov (United States)

    Gillet, Virginie; Hunting, Darel John; Takser, Larissa

    2016-09-01

    The prevention of neurodevelopmental disorders (NDD) of prenatal origin suffers from the lack of objective tools for early detection of susceptible individuals and the long time lag, usually in years, between the neurotoxic exposure and the diagnosis of mental dysfunction. Human data on the effects of alcohol, lead, and mercury and experimental data from animals on developmental neurotoxins and their long-term behavioral effects have achieved a critical mass, leading to the concept of the Developmental Origin of Health and Disease (DOHaD). However, there is currently no way to evaluate the degree of brain damage early after birth. We propose that extracellular vesicles (EVs) and particularly exosomes, released by brain cells into the fetal blood, may offer us a non-invasive means of assessing brain damage by neurotoxins. We are inspired by the strategy applied by Alan Turing (a cryptanalyst working for the British government), who created a first computer to decrypt German intelligence communications during World War II. Given the growing evidence that microRNAs (miRNAs), which are among the molecules carried by EVs, are involved in cell-cell communication, we propose that decrypting messages from EVs can allow us to detect damage thus offering an opportunity to cure, reverse, or prevent the development of NDD. This review summarizes recent findings on miRNAs associated with selected environmental toxicants known to be involved in the pathophysiology of NDD.

  10. Blood and Hair Mercury Concentrations in the Pacific Harbor Seal (Phoca vitulina richardii) Pup: Associations with Neurodevelopmental Outcomes.

    Science.gov (United States)

    Van Hoomissen, Samala; Gulland, Frances M D; Greig, Denise J; Castellini, J Margaret; O'Hara, Todd M

    2015-09-01

    Monomethylmercury (MeHg(+)) is an environmental pollutant, which at sufficiently high exposures, has induced neurotoxicosis in several animal species, including humans. Adverse neurological effects due to gestational exposure are of particular concern as MeHg(+) readily crosses the blood-brain and placental barriers. The degree to which environmental concentrations in marine prey affect free-living piscivorous wildlife, however, remains largely undetermined. We examined associations of gestational exposures to mercury on neurodevelopment and survival using hair and blood concentrations of total mercury ([THg]) in a stranded population of Pacific harbor seal pups from central California. A positive association was determined for the presence of abnormal neurological symptoms and increasing [THg] in blood (P = 0.04), but not hair. Neither hair nor blood [THg] was significantly associated with survival, or the neurodevelopmental milestone 'free-feeding', which was measured from the onset of hand-assisted feeding to the time at which pups were able to consume fish independently. Both hair and blood [THg] exceeded threshold values considered potentially toxic to humans and other mammalian wildlife species. The higher [THg] in blood associated with abnormal neurological symptoms may indicate an adverse effect of this pollutant on neurodevelopment in harbor seal pups. These data have broader implications with respect to human health and public policy as harbor seals and humans consume similar fish species, and it is possible that safeguard levels established for marine mammals could also extend to human populations that regularly consume fish.

  11. Joint Exposure to Chemical and Nonchemical Neurodevelopmental Stressors in U.S. Women of Reproductive Age in NHANES

    Directory of Open Access Journals (Sweden)

    Amanda M. Evans

    2014-04-01

    Full Text Available Lead (Pb and methyl mercury (MeHg are well established neurodevelopmental toxicants (NDTs, but joint exposure to chemical and nonchemical (e.g., maternal stress stressors has rarely been considered. We characterized exposure to Pb, MeHg and a measure of physiological dysregulation associated with chronic stress and examined race/ethnicity as a predictor of joint NDT exposure. Using data from the 2003−2004 NHANES, potential chronic stress exposure was estimated using allostatic load (AL, a quantitative measure of physiological dysregulation. A Hazard Index was calculated for joint exposure to Pb and MeHg (HINDT. Logistic regression was used to assess the relationship between an indicator of elevated joint NDT exposures (HINDT > 1 and race/ethnicity. The multivariate model was stratified by AL groups to examine effect measure modification. African American (adjusted odds ratio [OR] [95% confidence interval] = 2.2 [1.4, 3.3] and Mexican American (1.4 [0.7, 2.6] women were more likely to have an HINDT > 1 compared to Caucasian women. Chronic stress was identified as an effect measure modifier with the largest ORs among women with high AL scores (African Americans = 4.3 [2.0, 9.5]; Mexican Americans = 4.2 [1.3, 14.1]. Chronic stress was found to modify the association between elevated joint NDT exposure and race/ethnicity, highlighting the importance of evaluating chemical and nonchemical stressor exposures leading to a common endpoint.

  12. Neurodevelopmental delay among HIV-infected preschool children receiving antiretroviral therapy and healthy preschool children in Soweto, South Africa.

    Science.gov (United States)

    Lowick, Sarah; Sawry, Shobna; Meyers, Tammy

    2012-01-01

    Neurodevelopmental delay has been documented in up to 97.5% of HIV-infected children in Soweto who were not yet on antiretroviral treatment (ART). With growing numbers of children in South Africa being successfully treated with ART, the effects of ART on neurocognitive functioning in children require investigation. The objective of this study was to determine the extent of neurodevelopmental delay in stable HIV-infected preschool children (aged five to six years) receiving ART and compare it to an apparently healthy (unconfirmed HIV-status) group of preschool children. Thirty HIV-infected preschool children (virologically and immunologically stable on ART for more than one year) were conveniently sampled from 350 eligible children on ART at the Harriet Shezi Children's Clinic in Soweto, Johannesburg. The comparison group comprised 30 well-nourished preschool children attending the Lilian Ngoyi Primary Health Care Clinic in Soweto for routine immunizations. Each child was assessed using the Griffiths Mental Development Scales-Extended Revised Version (GMDS-ER), at a single point in time. The overall developmental z-scores on GMDS-ER were children in the HIV-infected group compared to 23 (76%) in the comparison group (p = 0.166). Mental handicap (overall GQ children in the HIV-infected group compared to 10% in the comparison group (p = 0.002). There was a 7.88-fold increased likelihood of severe delay in the HIV infected group. The HIV-infected group and comparison group had significantly different (p = 0.001) mean overall GQ scores of 70 (95% CI: 66.0-74.0) and 78 (95% CI: 75.6-80.5), respectively, with lower mean scores in the HIV-infected group in all individual domains. Early initiation of ART in HIV-infected infants may improve cognitive functioning among this group; however, intervention strategies which optimize early cognitive development for all children in the area need to be urgently considered.

  13. Structural cerebral abnormalities and neurodevelopmental status in single ventricle congenital heart disease before Fontan procedure.

    Science.gov (United States)

    Knirsch, Walter; Mayer, Kristina Nadine; Scheer, Ianina; Tuura, Ruth; Schranz, Dietmar; Hahn, Andreas; Wetterling, Kristina; Beck, Ingrid; Latal, Beatrice; Reich, Bettina

    2017-04-01

    Neonates with single ventricle congenital heart disease are at risk for structural cerebral abnormalities. Little is known about the further evolution of cerebral abnormalities until Fontan procedure. Between August 2012 and July 2015, we conducted a prospective cross-sectional two centre study using cerebral magnetic resonance imaging (MRI) and neuro-developmental outcome assessed by the Bayley-III. Forty-seven children (31 male) were evaluated at a mean age of 25.9 ± 3.4 months with hypoplastic left heart syndrome (25) or other single ventricle (22). Cerebral MRI was abnormal in 17 patients (36.2%) including liquor space enlargements (10), small grey (9) and minimal white (5) matter injuries. Eight of 17 individuals had combined lesions. Median (range) cognitive composite score (CCS) (100, 65-120) and motor composite score (MCS) (97, 55-124) were comparable to the reference data, while language composite score (LCS) (97, 68-124) was significantly lower ( P  = 0.040). Liquor space enlargement was associated with poorer performance on all Bayley-III subscores (CCS: P  = 0.02; LCS: P  = 0.002; MCS: P  = 0.013). The number of re-operations [odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1-4.3] ( P  = 0.03) and re-interventions (OR 2.1, 95% CI 1.1-3.8) ( P  = 0.03) was associated with a higher rate of overall MRI abnormalities. Cerebral MRI abnormalities occur in more than one third of children with single ventricle, while the neuro-developmental status is less severely affected before Fontan procedure. Liquor space enlargement is the predominant MRI finding associated with poorer neuro-developmental status, warranting further studies to determine aetiology and further evolution until school-age.

  14. Maternal obesity affects fetal neurodevelopmental and metabolic gene expression: a pilot study.

    Directory of Open Access Journals (Sweden)

    Andrea G Edlow

    Full Text Available OBJECTIVE: One in three pregnant women in the United States is obese. Their offspring are at increased risk for neurodevelopmental and metabolic morbidity. Underlying molecular mechanisms are poorly understood. We performed a global gene expression analysis of mid-trimester amniotic fluid cell-free fetal RNA in obese versus lean pregnant women. METHODS: This prospective pilot study included eight obese (BMI≥30 and eight lean (BMI<25 women undergoing clinically indicated mid-trimester genetic amniocentesis. Subjects were matched for gestational age and fetal sex. Fetuses with abnormal karyotype or structural anomalies were excluded. Cell-free fetal RNA was extracted from amniotic fluid and hybridized to whole genome expression arrays. Genes significantly differentially regulated in 8/8 obese-lean pairs were identified using paired t-tests with the Benjamini-Hochberg correction (false discovery rate of <0.05. Biological interpretation was performed with Ingenuity Pathway Analysis and the BioGPS gene expression atlas. RESULTS: In fetuses of obese pregnant women, 205 genes were significantly differentially regulated. Apolipoprotein D, a gene highly expressed in the central nervous system and integral to lipid regulation, was the most up-regulated gene (9-fold. Apoptotic cell death was significantly down-regulated, particularly within nervous system pathways involving the cerebral cortex. Activation of the transcriptional regulators estrogen receptor, FOS, and STAT3 was predicted in fetuses of obese women, suggesting a pro-estrogenic, pro-inflammatory milieu. CONCLUSION: Maternal obesity affects fetal neurodevelopmental and metabolic gene expression as early as the second trimester. These findings may have implications for postnatal neurodevelopmental and metabolic abnormalities described in the offspring of obese women.

  15. with neurodevelopmental

    African Journals Online (AJOL)

    clumsiness, mixed dominance or a specific learning disability. They correlated developmental milestones with seven levels of brainstem and cortical function and postulated that a block at any one of these levels precludes development of functions controlled by higher levels. This is caused by an interruption in the sensory ...

  16. Intragenic deletion of RBFOX1 associated with neurodevelopmental/neuropsychiatric disorders and possibly other clinical presentations

    Science.gov (United States)

    2013-01-01

    Background RBFOX1 is an important splicing factor regulating developmental and tissue-specific alternative splicing in heart, muscle, and neuronal tissues. Constitutional genetic defects in RBFOX1 are implicated in multiple medical conditions. Results We identified 14 copy number variants (CNV) involving RBFOX1 from 2,124 consecutive pediatric patients referred for chromosomal microarray analysis (CMA), including 13 intragenic deletions and a single intragenic duplication. The clinical significances of the intragenic deletions of RBFOX1 were evaluated. Conclusions Our data strongly supports the associations of intragenic deletions of RBFOX1 with a diversity of neurodevelopmental and neuropsychiatric disorders, and possibly other clinical features. PMID:23822903

  17. Treatments and services for neurodevelopmental disorders on advocacy websites: Information or evaluation?

    DEFF Research Database (Denmark)

    Di Pietro, Nina C; Whiteley, Louise Emma; Illes, Judy

    2011-01-01

    The Internet has quickly gained popularity as a major source of health-related information, but its impact is unclear. Here, we investigate the extent to which advocacy websites for three neurodevelopmental disorders—cerebral palsy (CP), autism spectrum disorder (ASD) and fetal alcohol spectrum...... disorder (FASD)—inform stakeholders about treatment options, and discuss the ethical challenges inherent in providing such information online. We identified major advocacy websites for each disorder and assessed website accountability, the number, attributes, and accessibility of treatments described...

  18. Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.

    Science.gov (United States)

    Reuter, Miriam S; Tawamie, Hasan; Buchert, Rebecca; Hosny Gebril, Ola; Froukh, Tawfiq; Thiel, Christian; Uebe, Steffen; Ekici, Arif B; Krumbiegel, Mandy; Zweier, Christiane; Hoyer, Juliane; Eberlein, Karolin; Bauer, Judith; Scheller, Ute; Strom, Tim M; Hoffjan, Sabine; Abdelraouf, Ehab R; Meguid, Nagwa A; Abboud, Ahmad; Al Khateeb, Mohammed Ayman; Fakher, Mahmoud; Hamdan, Saber; Ismael, Amina; Muhammad, Safia; Abdallah, Ebtessam; Sticht, Heinrich; Wieczorek, Dagmar; Reis, André; Abou Jamra, Rami

    2017-03-01

    Autosomal recessive inherited neurodevelopmental disorders are highly heterogeneous, and many, possibly most, of the disease genes are still unknown. To promote the identification of disease genes through confirmation of previously described genes and presentation of novel candidates and provide an overview of the diagnostic yield of exome sequencing in consanguineous families. Autozygosity mapping in families and exome sequencing of index patients were performed in 152 consanguineous families (the parents descended from a same ancestor) with at least 1 offspring with intellectual disability (ID). The study was conducted from July 1, 2008, to June 30, 2015, and data analysis was conducted from July 1, 2015, to August 31, 2016. Of the 152 consanguineous families enrolled, 1 child (in 45 families [29.6%]) or multiple children (107 families [70.4%]) had ID; additional features were present in 140 of the families (92.1%). The mean (SD) age of the children was 10.3 (9.0) years, and 171 of 297 (57.6%) were male. In 109 families (71.7%), potentially protein-disrupting and clinically relevant variants were identified. Of these, a clear clinical genetic diagnosis was made in 56 families (36.8%) owing to 57 (likely) pathogenic variants in 50 genes already established in neurodevelopmental disorders (46 autosomal recessive, 2 X-linked, and 2 de novo) or in 7 previously proposed recessive candidates. In 5 of these families, potentially treatable disorders were diagnosed (mutations in PAH, CBS, MTHFR, CYP27A1, and HIBCH), and in 1 family, 2 disease-causing homozygous variants in different genes were identified. In another 48 families (31.6%), 52 convincing recessive variants in candidate genes that were not previously reported in regard to neurodevelopmental disorders were identified. Of these, 14 were homozygous and truncating in GRM7, STX1A, CCAR2, EEF1D, GALNT2, SLC44A1, LRRIQ3, AMZ2, CLMN, SEC23IP, INIP, NARG2, FAM234B, and TRAP1. The diagnostic yield was higher in

  19. Elevated titanium levels in Iraqi children with neurodevelopmental disorders echo findings in occupation soldiers.

    Science.gov (United States)

    Savabieasfahani, M; Alaani, S; Tafash, M; Dastgiri, S; Al-Sabbak, M

    2015-01-01

    Anthropogenic release of pollutants into the environment is especially harmful to growing fetuses and young children. These populations are at an increased risk of damage because exposure to pollutants during critical periods of development can cause many impairments. Children's exposure to mixtures of metals could be responsible for the rising numbers of neurological disorders surfacing in Iraqi children. Titanium (Ti) and magnesium (Mg) are heavily used in war industries. Exposure to Ti and Mg has been linked to the dust in occupation soldiers' lungs. Hair samples of children in Hawija, Iraq (n = 13) contained significantly higher levels of Ti compared to Iranian children (n = 13) living near the Iraqi border (2080 ± 940 vs 707 ± 421 μg/kg, p children compared to Iranian children (115,763 ± 118,155 vs 67,650 ± 46,729 μg/kg). In samples from Hawija, Ti was 1.3 times higher in children with neurodevelopmental disorders (2198 ± 1108 vs 1942 ± 779 μg/kg), and Mg was 1.9 times higher in children without neurodevelopmental disorders (155,618 ± 140,791 vs 81,602 ± 91,940 μg/kg). Lead, arsenic, and cadmium in Hawija children with neurodevelopmental disorders (n = 6) were 2.5, 2.2, and 1.37 times higher compared to non-disabled children (n = 7). To get a clear understanding of the current status of neurodevelopmental disorders in Iraqi children and to determine the magnitude of this suspected global health issue, registries should be set up to compile and aggregate data from hospitals, clinics, and health centers across the country. Functional registries can develop collaborations with researchers toward finding causes of these disorders in Iraqi children and toward preventing them.

  20. PPREMO: a prospective cohort study of preterm infant brain structure and function to predict neurodevelopmental outcome.

    Science.gov (United States)

    George, Joanne M; Boyd, Roslyn N; Colditz, Paul B; Rose, Stephen E; Pannek, Kerstin; Fripp, Jurgen; Lingwood, Barbara E; Lai, Melissa M; Kong, Annice H T; Ware, Robert S; Coulthard, Alan; Finn, Christine M; Bandaranayake, Sasaka E

    2015-09-16

    More than 50 percent of all infants born very preterm will experience significant motor and cognitive impairment. Provision of early intervention is dependent upon accurate, early identification of infants at risk of adverse outcomes. Magnetic resonance imaging at term equivalent age combined with General Movements assessment at 12 weeks corrected age is currently the most accurate method for early prediction of cerebral palsy at 12 months corrected age. To date no studies have compared the use of earlier magnetic resonance imaging combined with neuromotor and neurobehavioural assessments (at 30 weeks postmenstrual age) to predict later motor and neurodevelopmental outcomes including cerebral palsy (at 12-24 months corrected age). This study aims to investigate i) the relationship between earlier brain imaging and neuromotor/neurobehavioural assessments at 30 and 40 weeks postmenstrual age, and ii) their ability to predict motor and neurodevelopmental outcomes at 3 and 12 months corrected age. This prospective cohort study will recruit 80 preterm infants born ≤ 30 week's gestation and a reference group of 20 healthy term born infants from the Royal Brisbane & Women's Hospital in Brisbane, Australia. Infants will undergo brain magnetic resonance imaging at approximately 30 and 40 weeks postmenstrual age to develop our understanding of very early brain structure at 30 weeks and maturation that occurs between 30 and 40 weeks postmenstrual age. A combination of neurological (Hammersmith Neonatal Neurologic Examination), neuromotor (General Movements, Test of Infant Motor Performance), neurobehavioural (NICU Network Neurobehavioural Scale, Premie-Neuro) and visual assessments will be performed at 30 and 40 weeks postmenstrual age to improve our understanding of the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks corrected age and motor and neurodevelopmental outcomes at 12 months corrected age

  1. The Integrated Status and Effectiveness Monitoring Program : Expansion of Existing Smolt Trapping Program and Steelhead Spawner Surveys : March 1st, 2008 - February 28th, 2009.

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Todd; Tonseth, Michael

    2009-01-01

    The Integrated Status and Effectiveness Monitoring Program (ISEMP - BPA project No.2003-0017) has been created as a cost effective means of developing protocols and new technologies, novel indicators, sample designs, analytical, data management and communication tools and skills, and restoration experiments that support the development of a region-wide Research, Monitoring and Evaluation (RME) program to assess the status of anadromous salmonid populations, their tributary habitat and restoration and management actions. The most straightforward approach to developing a regional-scale monitoring and evaluation program would be to increase standardization among status and trend monitoring programs. However, the diversity of species and their habitat, as well as the overwhelming uncertainty surrounding indicators, metrics, and data interpretation methods, requires the testing of multiple approaches. Thus, the approach ISEMP has adopted is to develop a broad template that may differ in the details among subbasins, but one that will ultimately lead to the formation of a unified RME process for the management of anadromous salmonid populations and habitat across the Columbia River Basin. ISEMP has been initiated in three pilot subbasins, the Wenatchee/Entiat, John Day, and Salmon. To balance replicating experimental approaches with the goal of developing monitoring and evaluation tools that apply as broadly as possible across the Pacific Northwest, these subbasins were chosen as representative of a wide range of potential challenges and conditions, e.g., differing fish species composition and life histories, ecoregions, institutional settings, and existing data. ISEMP has constructed a framework that builds on current status and trend monitoring infrastructures in these pilot subbasins, but challenges current programs by testing alternative monitoring approaches. In addition, the ISEMP is: (1) Collecting information over a hierarchy of spatial scales, allowing for a

  2. Participation of children with neurodevelopmental risk factors in the early rehabilitation program in relation to the level of parental education.

    Science.gov (United States)

    Mikelić, Valentina Matijević; Kosicek, Tena; Crnković, Maja; Radanović, Branko

    2011-12-01

    Many factors that have an adverse effect on fetal growth and development can manifest later in the child's development. Because of the biological basis, children born under the influence of these factors belong to the group of neurorisk children. They need special attention and prompt participation in the early rehabilitation program to encourage the use of brain plasticity. In addition to the biological influences, socioeconomic status affects a wide array of medical, cognitive and socio-emotional consequences in children, which begin before birth and continue into adulthood. This retrospective study included 50 children aged one to three years, hospitalized at Department of Pediatric Rehabilitation, University Department of Rheumatology, Physical Medicine and Rehabilitation, Sestre milosrdnice University Hospital Center in Zagreb. The aim was to determine the frequency of inclusion of children with neurodevelopmental risks in the early rehabilitation program according to the level of parental education. The results showed the highest percentage of parents of neurorisk children to have high school education, while the smallest number of parents had elementary school education. These data pointed to the lack of public awareness of the importance of the early period of life. However, they also indicated the lack of parental knowledge of their rights and opportunities for involvement of their neurorisk children in the early rehabilitation programs.

  3. A Dose-Response Relationship between Organic Mercury Exposure from Thimerosal-Containing Vaccines and Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    David A. Geier

    2014-09-01

    Full Text Available A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg exposure from thimerosal-containing (49.55% Hg by weight vaccines on the risk of neurodevelopmental disorders (NDs. Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991–2000 in the Vaccine Safety Datalink (VSD project. ND cases were diagnosed with pervasive developmental disorder (PDD, specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR = 1.054, specific developmental delay (OR = 1.035, tic disorder (OR = 1.034 and hyperkinetic syndrome of childhood (OR = 1.05 cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis.

  4. Motor Abnormalities: From Neurodevelopmental to Neurodegenerative Through "Functional" (Neuro)Psychiatric Disorders.

    Science.gov (United States)

    Peralta, Victor; Cuesta, Manuel J

    2017-09-01

    Motor abnormalities (MAs) of severe mental disorders have been traditionally neglected both in clinical practice and research, although they are an increasing focus of attention because of their clinical and neurobiological relevance. For historical reasons, most of the literature on MAs has been focused to a great extent on schizophrenia, and as a consequence their prevalence and featural properties in other psychiatric or neuropsychiatric disorders are poorly known. In this article, we evaluated the extent to which catatonic, extrapyramidal and neurological soft signs, and their associated clinical features, are present transdiagnostically. We examined motor-related features in neurodevelopmental (schizophrenia, obsessive compulsive disorder, autism spectrum disorders), "functional" (nonschizophrenic nonaffective psychoses, mood disorders) and neurodegenerative (Alzheimer's disease) disorders. Examination of the literature revealed that there have been very few comparisons of motor-related features across diagnoses and we had to rely mainly in disorder-specific studies to compare it transdiagnostically. One or more motor domains had a substantial prevalence in all the diagnoses examined. In "functional" disorders, MAs, and particularly catatonic signs, appear to be markers of episode severity; in chronic disorders, although with different degree of strength or evidence, all motor domains are indicators of both disorder severity and poor outcome; lastly, in Alzheimer's disease they are also indicators of disorder progression. MAs appear to represent a true transdiagnostic domain putatively sharing neurobiological mechanisms of neurodevelopmental, functional or neurodegenerative origin.

  5. Social cognition and neural substrates of face perception: implications for neurodevelopmental and neuropsychiatric disorders.

    Science.gov (United States)

    Lazar, Steven M; Evans, David W; Myers, Scott M; Moreno-De Luca, Andres; Moore, Gregory J

    2014-04-15

    Social cognition is an important aspect of social behavior in humans. Social cognitive deficits are associated with neurodevelopmental and neuropsychiatric disorders. In this study we examine the neural substrates of social cognition and face processing in a group of healthy young adults to examine the neural substrates of social cognition. Fifty-seven undergraduates completed a battery of social cognition tasks and were assessed with electroencephalography (EEG) during a face-perception task. A subset (N=22) were administered a face-perception task during functional magnetic resonance imaging. Variance in the N170 EEG was predicted by social attribution performance and by a quantitative measure of empathy. Neurally, face processing was more bilateral in females than in males. Variance in fMRI voxel count in the face-sensitive fusiform gyrus was predicted by quantitative measures of social behavior, including the Social Responsiveness Scale (SRS) and the Empathizing Quotient. When measured as a quantitative trait, social behaviors in typical and pathological populations share common neural pathways. The results highlight the importance of viewing neurodevelopmental and neuropsychiatric disorders as spectrum phenomena that may be informed by studies of the normal distribution of relevant traits in the general population. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Tourette Syndrome and Learning Disabilities: a focus on correlations in a neurodevelopmental perspective

    Directory of Open Access Journals (Sweden)

    Brambilla Emma

    2016-04-01

    Full Text Available People with Tourette Syndrome (TS frequently show the presence of Learning Disabilities (LD at school age. Literature investigating the correlation between TS and LD is limited: studies focus on the incidence of this correlation, the impact on school achievement and the number of fields affected by these difficulties, show neuropsychological diseases in comorbility and reveal a discrepancy between IQ scores and school results. The most important evidence shows that in some children the appearance of LD and tics coincide. In a neurodevelopmental approach, the origin of both symptoms, TS and LD, can be explained observing the nervous system’s maturation process, through specific steps, which lead to the acquisition of visual, aural and tactile competence, and allow the development of mobility, language and manual ability. As they all develop along a continuum, neurodevelopmental levels that have not been completed always imply neuro-functional anomalies, which can be observed with brain-imaging techniques. Investigating this correlation in a neuropsychological perspective would be useful not only to better understand the underlying functional aspects, but also to properly plan good rehabilitation strategies to apply in everyday clinical practice.

  7. Neurodevelopmental variability in three young girls with a rare chromosomal disorder, 48, XXXX.

    Science.gov (United States)

    Samango-Sprouse, Carole; Keen, Colleen; Mitchell, Francie; Sadeghin, Teresa; Gropman, Andrea

    2015-10-01

    Fourty eight, XXXX is a rare chromosomal aneuploidy associated with neurocognitive deficits, speech and language disorders and executive dysfunction but the scarcity and variability of reported cases limit our understanding of the 48, XXXX phenotype. To our knowledge, this is the first study to report on the neurodevelopmental profile of three young females with 48, XXXX. Patient 1 (age = 11.0), Patient 2 (age = 10.9), and Patient 3 (age = 6.4) were evaluated using comprehensive neurodevelopmental assessments. Parent questionnaires were completed to assess behavioral and psychosocial domains including executive function, ADHD and anxiety. Nonverbal intelligence quotients were 56, 80, and 91 for Patients 1, 2, and 3, respectively. There were significantly impaired visual motor capacities in graphomotor and perceptual domains below the 5th centile in Patients 1 and 2, and mildly impaired visual perception skills in Patient 3. All three patients had Childhood Apraxia of Speech (CAS) but of varying severity and similar executive dysfunction, externalizing problems and social difficulties. Familial learning disabilities (FLD) in Patient 1 and the co-occurrence of ADHD in Patient's 1 and 2 may contribute to their more impaired cognitive performances relative to Patient 3 who is the second reported case of 48, XXXX to have normal intellect. These distinct and overlapping characteristics expand the phenotypic profile of 48, XXXX and may be used in the counseling of families and treatment of children with 48, XXXX. © 2015 Wiley Periodicals, Inc.

  8. Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy.

    Science.gov (United States)

    Raine, Adrian; Lee, Lydia; Yang, Yaling; Colletti, Patrick

    2010-09-01

    Antisocial personality disorder and psychopathy have been hypothesised to have a neurodevelopmental basis, but this proposition has not been formally tested. This study tests the hypothesis that individuals with cavum septum pellucidum (CSP), a marker of limbic neural maldevelopment, will show higher levels of psychopathy and antisocial personality. Cavum septum pellucidum was assessed using anatomical magnetic resonance imaging in a community sample. Those with CSP (n = 19) were compared with those lacking CSP (n = 68) on antisocial personality, psychopathy and criminal offending. Those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. The pervasiveness of this association was indicated by the fact that those lacking a diagnosis of antisocial personality disorder, but who were charged or convicted for an offence, had a more extensive CSP than non-antisocial controls. Results could not be attributed to prior trauma exposure, head injury, demographic factors or comorbid psychiatric conditions. Our findings appear to be the first to provide evidence for a neurodevelopmental brain abnormality in those with antisocial personality disorder and psychopathy, and support the hypothesis that early maldevelopment of limbic and septal structures predisposes to the spectrum of antisocial behaviours.

  9. Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population.

    Science.gov (United States)

    Glans, Martin; Bejerot, Susanne; Humble, Mats B

    2017-09-01

    Generalised joint hypermobility (GJH) is reportedly overrepresented among clinical cases of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and developmental coordination disorder (DCD). It is unknown if these associations are dimensional and, therefore, also relevant among non-clinical populations. To investigate if GJH correlates with sub-syndromal neurodevelopmental symptoms in a normal population. Hakim-Grahame's 5-part questionnaire (5PQ) on GJH, neuropsychiatric screening scales measuring ADHD and ASD traits, and a DCD-related question concerning clumsiness were distributed to a non-clinical, adult, Swedish population ( n =1039). In total, 887 individuals met our entry criteria. We found no associations between GJH and sub-syndromal symptoms of ADHD, ASD or DCD. Although GJH is overrepresented in clinical cases with neurodevelopmental disorders, such an association seems absent in a normal population. Thus, if GJH serves as a biomarker cutting across diagnostic boundaries, this association is presumably limited to clinical populations. None. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

  10. Gluten Intolerance and Neurodevelopmental Disorders: Is Nitric Oxide the Common Biomarker Linking These Conditions?

    Science.gov (United States)

    Fluegge, Keith

    2016-01-01

    Cruchet et al. attempt to tease out the myths and facts surrounding the growing popularity of certain dietary approaches in the management of neurodevelopmental disorders, like attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs). The authors identify a particular exclusionary-type approach that seeks to eliminate dietary gluten. Although the relationship between celiac disease (CD) and ADHD/ASD is not well established, a repeated clinical feature noted in CD is the elevated levels of nitric oxide in serum and urine. Elevated oxidative stress has also been observed in neurodevelopmental conditions, and the author of this correspondence has been the first to propose that chronic, environmental exposure to the air pollutant, nitrous oxide may contribute to these oxidative stress profiles through neural cholinergic perturbation. Therefore, the purpose of this correspondence is to highlight this biochemical connection between these conditions so as to identify the clinical populations who may realize the greatest benefit of these dietary approaches, while minimizing any potential risk of nutrient deficiencies. © 2016 S. Karger AG, Basel.

  11. Prevalence and comorbidities of autism among children referred to the outpatient clinics for neurodevelopmental disorders.

    Science.gov (United States)

    Mpaka, Davin Mbeya; Okitundu, Daniel Luwa E-Andjafono; Ndjukendi, Ally Omba; N'situ, Adelin Mankubu; Kinsala, Sebastien Yabassi; Mukau, Joachim Ebwel; Ngoma, Valentin Malanda; Kashala-Abotnes, Espérance; Ma-Miezi-Mampunza, Samuel; Vogels, Annick; Steyaert, Jeans

    2016-01-01

    Autism spectrum disorders (ASD) is a neurodevelopmental disorder that has been rarely diagnosed in Sub-Saharan Africa. Although a proportion of children do present features of ASD in the Democratic Republic of Congo (DRC), little is known about it prevalence. Often, the co-morbidities constitute the upfront symptoms and therefore may it recognition and management difficult, aggravating as such the prognosis. The present study therefore aimed at studying the clinical profile of autism spectrum disorder (ASD) and the associated morbidities among children and adolescents in outpatient clinics in Kinshasa, the Democratic Republic of Congo. We conducted a cross sectional study in the three outpatients centers receiving patients referred for neurodevelopmental disorders in Kinshasa, DRC, from June 2008 to June 2010. A total of 450 subjects aged from 1-18 years old were referred and included in the study. The clinical diagnosis for ASD was made using the DSM-IV-R and the ADIR. Co-morbidities were identified using DSM-IV-R criteria together with an extensive clinical interview and observation. All patients were subject to an intellectual quotient evaluation and an electroencephalogram reporting. Of the 450 subjects referred, 120 (29.3%) received the diagnosis of ASD, with boys outnumbering girls (OR 3:1. The mean age was 7.9 years (SD 3.4) (psociety in Kinshasa DRC. This will help to identify and manage ASD and associated co-morbidities at an early stage for a better prognosis.

  12. Rapamycin prevents seizures after depletion of STRADA in a rare neurodevelopmental disorder.

    Science.gov (United States)

    Parker, Whitney E; Orlova, Ksenia A; Parker, William H; Birnbaum, Jacqueline F; Krymskaya, Vera P; Goncharov, Dmitry A; Baybis, Marianna; Helfferich, Jelte; Okochi, Kei; Strauss, Kevin A; Crino, Peter B

    2013-04-24

    A rare neurodevelopmental disorder in the Old Order Mennonite population called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome; also called Pretzel syndrome) is characterized by infantile-onset epilepsy, neurocognitive delay, craniofacial dysmorphism, and histopathological evidence of heterotopic neurons in subcortical white matter and subependymal regions. PMSE is caused by a homozygous deletion of exons 9 to 13 of the LYK5/STRADA gene, which encodes the pseudokinase STRADA, an upstream inhibitor of mammalian target of rapamycin complex 1 (mTORC1). We show that disrupted pathfinding in migrating mouse neural progenitor cells in vitro caused by STRADA depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki). We demonstrate that rapamycin can rescue aberrant cortical lamination and heterotopia associated with STRADA depletion in the mouse cerebral cortex. Constitutive mTORC1 signaling and a migration defect observed in fibroblasts from patients with PMSE were also prevented by mTORC1 inhibition. On the basis of these preclinical findings, we treated five PMSE patients with sirolimus (rapamycin) without complication and observed a reduction in seizure frequency and an improvement in receptive language. Our findings demonstrate a mechanistic link between STRADA loss and mTORC1 hyperactivity in PMSE, and suggest that mTORC1 inhibition may be a potential treatment for PMSE as well as other mTOR-associated neurodevelopmental disorders.

  13. Stabilizing autism: A Fleckian account of the rise of a neurodevelopmental spectrum disorder.

    Science.gov (United States)

    Verhoeff, Berend

    2014-06-01

    Using the conceptual tools of philosopher of science Ludwik Fleck, I argue that the reframing of autism as a neurodevelopmental spectrum disorder is constrained by two governing 'styles of thought' of contemporary psychiatry. The first is the historically conditioned 'readiness for directed perception' of, and thinking in terms of, ontologically distinct diseases. The clinical gaze of mental health professionals, the bureaucratic needs of health administration, the clinical and scientific utility of disease categories, and the practices of autism-oriented advocacy groups all imply a bias toward thinking about autism and related disorders as ontologically distinct psychiatric and scientific entities. Second, within the 'neuromolecular style of thought', mental disorders are more and more located at the neurobiological levels of the brain. In autism research, one of the biggest challenges is the identification of autism's neurobiological singularity. However, at a moment when biological and categorical approaches toward autism face serious empirical difficulties, a balance is established that holds together these two styles of thought. With a need to account for some of the most persistent uncertainties and conflicts in autism research, namely ubiquitous heterogeneity and a failure to identify disease specific biomarkers, the reframing of autism as a neurodevelopmental spectrum disorder satisfies the scientific, institutional and socio-political needs for stability and homogenization. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. "Selfish spermatogonial selection": a novel mechanism for the association between advanced paternal age and neurodevelopmental disorders.

    Science.gov (United States)

    Goriely, Anne; McGrath, John J; Hultman, Christina M; Wilkie, Andrew O M; Malaspina, Dolores

    2013-06-01

    There is robust evidence from epidemiological studies that the offspring of older fathers have an increased risk of neurodevelopmental disorders, such as schizophrenia and autism. The authors present a novel mechanism that may contribute to this association. Because the male germ cell undergoes many more cell divisions across the reproductive age range, copy errors taking place in the paternal germline are associated with de novo mutations in the offspring of older men. Recently it has been recognized that somatic mutations in male germ cells that modify proliferation through dysregulation of the RAS protein pathway can lead to within-testis expansion of mutant clonal lines. First identified in association with rare disorders related to paternal age (e.g., Apert syndrome, achondroplasia), this process is known as "selfish spermatogonial selection." This mechanism favors propagation of germ cells carrying pathogenic mutations, increasingly skews the mutational profile of sperm as men age, and enriches de novo mutations in the offspring of older fathers that preferentially affect specific cellular signaling pathways. This mechanism not only offers a parsimonious explanation for the association between advanced paternal age and various neurodevelopmental disorders but also provides insights into the genetic architecture (role of de novo mutations), neurobiological correlates (altered cell cycle), and some epidemiological features of these disorders. The authors outline hypotheses to test this model. Given the secular changes for delayed parenthood in most societies, this hypothesis has important public health implications.

  15. Dermatoglyphics--a possible biomarker in the neurodevelopmental model for the origin of mental disorders.

    Science.gov (United States)

    Ahmed-Popova, Ferihan M; Mantarkov, Mladen J; Sivkov, Stefan T; Akabaliev, Valentin H

    2014-01-01

    Dermatoglyphic pattern formation and differentiation are complex processes which have been in the focus of research interest ever since dermatoglyphics became a science. The patterns' early differentiation and genetic uniqueness as well as the relatively simple methods used to obtain and store fingerprints make it possible to study the relationship between certain dermatoglyphic characteristics and the underlying pathological processes in a number of diseases, including mental disorders. The present review reports published data from fundamental and clinical studies on dermatoglyphics primarily in schizophrenia and bipolar disorder to lend additional support for the neurodevelopmental hypothesis in the etiology of these disorders. Following an analysis of the theories of dermatoglyphics formation and the complex association between ridge patterns and central nervous system in early embryogenesis, an attempt is made to present dermatoglyphics as possible biological markers of impaired neurodevelopment. The contradictory data in the literature on dermatoglyphics in mental disorders suggest the need for further studies on these biological markers in order to identify their place in the neurodevelopmental etiological model of these diseases.

  16. HIV-associated neurodevelopmental delay: prevalence, predictors and persistence in relation to antiretroviral therapy initiation and viral suppression.

    Science.gov (United States)

    Strehlau, R; Kuhn, L; Abrams, E J; Coovadia, A

    2016-11-01

    HIV infection in infancy may influence the developing brain, leading to adverse neurodevelopmental consequences. We aim to describe neurodevelopmental characteristics of a cohort of HIV-infected infants and young children prior to antiretroviral therapy (ART) initiation and after achieving viral suppression. As part of the Neverest 2 trial, 195 HIV-infected children under 2 years of age were assessed using the Ages and Stages Questionnaire (ASQ) prior to ART initiation and at subsequent age-appropriate time points after ART had been started. The ASQ is a simple screening questionnaire used to identify children at risk of neurodevelopmental delays. Questionnaires completed by the parent/caregiver assess neurodevelopmental functioning in five domains: communication, gross motor, fine motor, problem solving and personal-social. Median age pre-ART was 8.8 months (range 2.2-24.9) and 53.9% were male. Mean time to viral suppression was 9.4 months (range 5.9-14.5). Compared with pre-ART better outcomes were reported at time of viral suppression with a lower proportion of children failing the gross motor (31.5% vs. 13%, p = 0.0002), fine motor (21.3% vs. 10.2%, p = 0.017), problem solving (26.9% vs. 9.3%, p = 0.0003) and personal-social (19.6% vs. 7.4%, p = 0.019) domains. However, there was no change in the communication domain (14.8% vs. 12.0%, p = 0.6072). Although achieving viral suppression on ART resulted in significant improvements in markers of neurodevelopmental function of young HIV-infected children, potential neurodevelopmental delays still persisted in a large proportion. Further interventions are needed to limit potential disabilities and maximize developmental outcomes. © 2016 John Wiley & Sons Ltd.

  17. Existence and Detection of Fireballs,

    Science.gov (United States)

    An attempt is made to analyze critically the experimental proofs indicating the existence of fireballs. Some ideas are presented on methods of the...properties of fireballs if their existence will be checked by other methods. (Author)

  18. Why do interstellar grains exist?

    Science.gov (United States)

    Seab, C. G.; Hollenbach, D. J.; Mckee, C. F.; Tielens, Alexander G. G. M.

    1986-01-01

    There exists a discrepancy between calculated destruction rates of grains in the interstellar medium and postulated sources of new grains. This problem was examined by modelling the global life cycle of grains in the galaxy. The model includes: grain destruction due to supernovae shock waves; grain injection from cool stars, planetary nebulae, star formation, novae, and supernovae; grain growth by accretion in dark clouds; and a mixing scheme between phases of the interstellar medium. Grain growth in molecular clouds is considered as a mechanism or increasing the formation rate. To decrease the shock destruction rate, several new physical processes, such as partial vaporization effects in grain-grain collisions, breakdown of the small Larmor radius approximation for betatron acceleration, and relaxation of the steady-state shock assumption are included.

  19. Relationship between Proton Magnetic Resonance Spectroscopy of Frontoinsular Gray Matter and Neurodevelopmental Outcomes in Very Low Birth Weight Children at the Age of 4.

    Directory of Open Access Journals (Sweden)

    Wojciech Durlak

    Full Text Available Very low birth weight is associated with long term neurodevelopmental complications. Macroscopic brain abnormalities in prematurity survivors have been investigated in several studies. However, there is limited data regarding local cerebral metabolic status and neurodevelopmental outcomes. The purpose of this study was to characterize the relationship between proton magnetic resonance spectra in basal ganglia, frontal white matter and frontoinsular gray matter, neurodevelopmental outcomes assessed with the Leiter scale and the Developmental Test of Visual Perception and selected socioeconomic variables in a cohort of very low birth weight children at the age of four. Children were divided in three groups based on the severity of neurodevelopmental impairment. There were no differences in spectroscopy in basal ganglia and frontal white matter between the groups. Lower concentrations of N-acetylaspartate (NAA, choline (Cho and myoinositol (mI were observed in the frontoinsular cortex of the left hemisphere in children with neurodevelopmental impairment compared to children with normal neurodevelopmental outcomes. Higher parental education, daycare attendance and breastfeeding after birth were associated with more favorable neurodevelopmental prognosis, whereas rural residence was more prevalent in children with moderate and severe impairment. Our study demonstrates the role of long term neurometabolic disruption in the left frontoinsular cortex and selected socioeconomic variables in determination of neurodevelopmental prognosis in prematurity survivors.

  20. Identification and functional characterization of de novo FOXP1 variants provides novel insights into the etiology of neurodevelopmental disorder.

    Science.gov (United States)

    Sollis, Elliot; Graham, Sarah A; Vino, Arianna; Froehlich, Henning; Vreeburg, Maaike; Dimitropoulou, Danai; Gilissen, Christian; Pfundt, Rolph; Rappold, Gudrun A; Brunner, Han G; Deriziotis, Pelagia; Fisher, Simon E

    2016-02-01

    De novo disruptions of the neural transcription factor FOXP1 are a recently discovered, rare cause of sporadic intellectual disability (ID). We report three new cases of FOXP1-related disorder identified through clinical whole-exome sequencing. Detailed phenotypic assessment confirmed that global developmental delay, autistic features, speech/language deficits, hypotonia and mild dysmorphic features are core features of the disorder. We expand the phenotypic spectrum to include sensory integration disorder and hypertelorism. Notably, the etiological variants in these cases include two missense variants within the DNA-binding domain of FOXP1. Only one such variant has been reported previously. The third patient carries a stop-gain variant. We performed functional characterization of the three missense variants alongside our stop-gain and two previously described truncating/frameshift variants. All variants severely disrupted multiple aspects of protein function. Strikingly, the missense variants had similarly severe effects on protein function as the truncating/frameshift variants. Our findings indicate that a loss of transcriptional repression activity of FOXP1 underlies the neurodevelopmental phenotype in FOXP1-related disorder. Interestingly, the three novel variants retained the ability to interact with wild-type FOXP1, suggesting these variants could exert a dominant-negative effect by interfering with the normal FOXP1 protein. These variants also retained the ability to interact with FOXP2, a paralogous transcription factor disrupted in rare cases of speech and language disorder. Thus, speech/language deficits in these individuals might be worsened through deleterious effects on FOXP2 function. Our findings highlight that de novo FOXP1 variants are a cause of sporadic ID and emphasize the importance of this transcription factor in neurodevelopment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email

  1. Facilitating support groups for siblings of children with neurodevelopmental disorders using audio-conferencing: a longitudinal feasibility study.

    Science.gov (United States)

    Gettings, Sheryl; Franco, Fabia; Santosh, Paramala J

    2015-01-01

    Siblings of children with chronic illness and disabilities are at increased risk of negative psychological effects. Support groups enable them to access psycho-education and social support. Barriers to this can include the distance they have to travel to meet face-to-face. Audio-conferencing, whereby three or more people can connect by telephone in different locations, is an efficient means of groups meeting and warrants exploration in this healthcare context. This study explored the feasibility of audio-conferencing as a method of facilitating sibling support groups. A longitudinal design was adopted. Participants were six siblings (aged eight to thirteen years) and parents of children with complex neurodevelopmental disorders attending the Centre for Interventional Paediatric Psychopharmacology (CIPP). Four of the eight one-hour weekly sessions were held face-to-face and the other four using audio-conferencing. Pre- and post-intervention questionnaires and interviews were completed and three to six month follow-up interviews were carried out. The sessions were audio-recorded, transcribed and thematic analysis was undertaken. Audio-conferencing as a form of telemedicine was acceptable to all six participants and was effective in facilitating sibling support groups. Audio-conferencing can overcome geographical barriers to children being able to receive group therapeutic healthcare interventions such as social support and psycho-education. Psychopathology ratings increased post-intervention in some participants. Siblings reported that communication between siblings and their family members increased and siblings' social network widened. Audio-conferencing is an acceptable, feasible and effective method of facilitating sibling support groups. Siblings' clear accounts of neuropsychiatric symptoms render them reliable informants. Systematic assessment of siblings' needs and strengthened links between Child and Adolescent Mental Health Services, school counsellors and

  2. Long-term neurodevelopmental outcome of monochorionic and matched dichorionic twins.

    Directory of Open Access Journals (Sweden)

    Karien E A Hack

    Full Text Available BACKGROUND: Monochorionic (MC twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS or intrauterine co-twin death or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC twins at the age of two years. METHODS: This was a prospective cohort study. Cerebral palsy (CP was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (unalikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner. FINDINGS: Four out of 182 MC infants had CP (2.2% - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5-38.2 of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7% had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0-1.4. Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its

  3. Autism spectrum disorder in a community-based sample with neurodevelopmental problems in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Yewande O. Oshodi

    2017-01-01

    Full Text Available Autism Spectrum Disorder (ASD is a globally prevalent neurodevelopmental disorder for which early diagnosis and intervention is the mainstay of management. In the African continent, limited data is available regarding the non-clinic based samples. Lack of information available to caregivers and inadequate skilled manpower often limit early detection and access to the few available though under resourced services in the community. Community based screening can be an important drive to create awareness and improve information dissemination regarding services available for those living with this disorder. This is a descriptive cross-sectional study utilizing data obtained from participants of a community-based autism screening exercise. The surveillance exercise was part of the annual Orange Ribbon initiative for autism awareness and screening held in 2014. Data was obtained from 85 participants involved in the Autism Surveillance screening exercise within the Lagos community. Community public service radio announcements state wide and word of mouth were used to invite and enroll eligible participants to the screening and consultation exercise. A second stage screening and a brief sociodemographic questionnaire followed by a third stage clinical interview and evaluation using the Diagnostic and Statistical Manual of Mental Disorders - 5 Edition (DSM 5 were used. Appropriate consultation and referrals to services in the community were given. Participants had a mean age of 7.53 years (SD 4.35. Twenty-nine (34.5% met the diagnosis of ASD. Other diagnosis included attention deficit hyperactivity disorder (ADHD, language and speech disorder, intellectual disability (8.3% and learning disorders (9.5%. Main health concerns to caregivers were poor language development in all (100%, of which 11 (40.7% were non-verbal; gaze avoidance was seen in 14 (48.3% and challenging behavior in 12 (42.9%. Comorbidities included seizure disorders (3.4% and ADHD (6

  4. Kierkegaardovo pojetí existence

    OpenAIRE

    Janatová, Kristýna

    2016-01-01

    The topic of the bachelor thesis is "Kierkegaard's conception of existence". There are both the life of the Danish philosopher Søren Kierkegaard and his philosophy discussed. The issue of human existence is analysed with its main three stages which are focused on aesthetics, ethics and religion. These stages of existence are at first described and afterwards compared with each other. The aesthetic represents the first stage of life and the religious stage is considered to be the highest aim o...

  5. Learning curve analyses in neurodevelopmental disorders: are children with autism spectrum disorder truly visual learners?

    Science.gov (United States)

    Erdődi, Lászlό; Lajiness-O'Neill, Renée; Schmitt, Thomas A

    2013-04-01

    Visual and auditory verbal learning using a selective reminding format was studied in a mixed clinical sample of children with autism spectrum disorder (ASD) (n = 42), attention-deficit hyperactivity disorder (n = 83), velocardiofacial syndrome (n = 17) and neurotypicals (n = 38) using the Test of Memory and Learning to (1) more thoroughly characterize and examine the integrity of learning and memory processes, (2) to better understand the mechanisms of learning impairment, and (3) to inform instructional practices in ASD. Contrary to expectations, children with ASD demonstrated a relative weakness in the rate of acquisition of visual in contrast to verbal learning compared to neurotypicals. They also showed a complex pattern of consolidation. Overall, between-group differences were more likely to emerge during the visual learning task, suggesting that it may be more sensitive for detecting neurodevelopmental differences. The heuristic value of assessing memory and learning across multiple trials and comparing performance during immediate and delayed recall is discussed.

  6. Premorbid multivariate markers of neurodevelopmental instability in the prediction of adult schizophrenia-spectrum disorder

    DEFF Research Database (Denmark)

    Golembo-Smith, Shana; Schiffman, Jason; Kline, Emily

    2012-01-01

    of 265 Danish children in 1972, when participants were 10-13years old. Parent psychiatric diagnoses were also obtained in order to evaluate the predictive strength of neurodevelopmental factors in combination with genetic risk. Adult diagnostic information was available for 244 members of the sample...... included minor physical anomalies (MPAs), coordination, ocular alignment, laterality, and IQ. Adult diagnoses were assessed through psychiatric interviews in 1992, as well as through a scan of the national psychiatric registry through 2007. Through a combination of multiple childhood predictors, the model...... correctly classified 73% (24 of 33) of the participants who eventually developed a schizophrenia-spectrum outcome in adulthood. Results suggest that, with replication, multivariate premorbid prediction could potentially be a useful complementary approach to identifying individuals at risk for developing...

  7. Both Low Blood Glucose and Insufficient Treatment Confer Risk of Neurodevelopmental Impairment in Congenital Hyperinsulinism

    DEFF Research Database (Denmark)

    Rasmussen, Annett Helleskov; Melikyan, Maria; Globa, Evgenia

    2017-01-01

    BACKGROUND/AIMS: Congenital hyperinsulinism (CHI) is a heterogeneous disease most frequently caused by KATP-channel (ABCC8 and KCNJ11) mutations, with neonatal or later onset, variable severity, and with focal or diffuse pancreatic involvement as the two major histological types. CHI confers a high.......023; and treatment delay from first symptom to expert center >5 days; OR 4.0 (1.0-16.6), trend p = 0.05. In multivariate analysis (n = 31) for early predictors with exclusion of brain MRI, treatment delay from first symptom to expert center >5 days conferred a significantly increased risk of neurodevelopment...... seen in uni- or multivariate analysis. CONCLUSION: Not only very low blood glucose, but also insufficient treatment as expressed by delay until expert center hospitalization, increased the risk of neurodevelopmental impairment. This novel finding calls for improvements in spread of knowledge about CHI...

  8. Haploinsufficiency of NR4A2 is associated with a neurodevelopmental phenotype with prominent language impairment.

    Science.gov (United States)

    Reuter, Miriam S; Krumbiegel, Mandy; Schlüter, Gregor; Ekici, Arif B; Reis, André; Zweier, Christiane

    2017-08-01

    Non-recurrent deletions in 2q24.1, minimally overlapping two genes, NR4A2 and GPD2, were recently described in individuals with language impairment and behavioral and cognitive symptoms. We herewith report on a female patient with a similar phenotype of severe language and mild cognitive impairment, in whom we identified a de novo deletion covering only NR4A2. NR4A2 encodes a transcription factor highly expressed in brain regions critical for speech and language and implicated in dopaminergic neuronal development. Our findings of a de novo deletion of NR4A2 in an individual with mild intellectual disability and prominent speech and language impairment provides further evidence for NR4A2 haploinsufficiency being causative for neurodevelopmental and particularly language phenotypes. © 2017 Wiley Periodicals, Inc.

  9. Communication Intervention for Young Children with Severe Neurodevelopmental Disabilities Via Telehealth.

    Science.gov (United States)

    Simacek, Jessica; Dimian, Adele F; McComas, Jennifer J

    2017-03-01

    Young children with neurodevelopmental disorders such as autism spectrum disorders (ASD) and Rett syndrome often experience severe communication impairments. This study examined the efficacy of parent-implemented communication assessment and intervention with remote coaching via telehealth on the acquisition of early communication skills of three young children with ASD (2) and Rett syndrome (1). Efficacy of the intervention was evaluated using single-case experimental designs. First, functional assessment was used to identify idiosyncratic/potentially communicative responses and contexts for each child. Next, parents implemented functional communication training (FCT). All of the children acquired the targeted communication responses. The findings support the efficacy of telehealth as a service delivery model to coach parents on intervention strategies for their children's early communication skills.

  10. Etiological Analysis of Neurodevelopmental Disabilities: Single-Center Eight-Year Clinical Experience in South China

    Directory of Open Access Journals (Sweden)

    Li Guo

    2011-01-01

    Full Text Available Etiology determination of neurodevelopmental disabilities (NDDs currently remains a worldwide common challenge on child health. We herein reported the etiology distribution feature in a cohort of 285 Chinese patients with NDDs. Although concrete NDD etiologies in 48.4% of the total patients could not be identified, genetic diseases (with the proportion of 35.8% in the total cases including inborn errors of metabolism (IEM and congenital dysmorphic diseases, constituted the commonest etiology category for NDDs in this study. The two key experimental technologies in pediatric metabolomics, gas chromatography-mass spectrometry (GC-MS, and tandem mass spectrometry (MS-MS, proved to be substantially helpful for the exploration of the NDD etiologies in this clinical investigation. The findings in this paper provided latest epidemiologic information on the etiology distribution of NDDs in Chinese, and the syndromic NDDs caused by citrin deficiency and the novel chromosomal karyotype, respectively, further expanded the etiology spectrum of NDDs.

  11. An Investigation of Bilateral Isokinematic Training and Neurodevelopmental Therapy in Improving Use of the Affected Hand in Children with Hemiplegia

    Science.gov (United States)

    Sheppard, Loretta; Mudie, Heather; Froude, Elspeth

    2007-01-01

    Motor impairment in children with hemiplegic cerebral palsy leads to a predominance of use of the unaffected hand. This impedes development of bimanual skills and deprives the affected side of the stimulus needed for normal growth. Occupational therapists aim to improve use of the affected hand, traditionally using Neurodevelopmental Therapy.…

  12. Neonatal Gram Negative and Candida Sepsis Survival and Neurodevelopmental Outcome at the Corrected Age of 24 Months

    NARCIS (Netherlands)

    T.R. de Haan (Timo Robert); L. Beckers (Loes); R.C.J. de Jonge (Rogier); L. Spanjaard (Lodewijk); L. van Toledo (Letty); D. Pajkrt (Dasja); A.G. van Wassenaer (Aleid); J.H. van der Lee (Johanna)

    2013-01-01

    textabstractObjectives: To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis. Methods: Historical cohort study in a population of

  13. An optimized gene set for transcriptomics based neurodevelopmental toxicity prediction in the neural embryonic stem cell test

    NARCIS (Netherlands)

    Pennings, J.L.A.; Theunissen, P.T.; Piersma, A.H.|info:eu-repo/dai/nl/071276947

    2012-01-01

    The murine neural embryonic stem cell test (ESTn) is an in vitro model for neurodevelopmental toxicity testing. Recent studies have shown that application of transcriptomics analyses in the ESTn is useful for obtaining more accurate predictions as well as mechanistic insights. Gene expression

  14. Genetic and pharmacological manipulations of the serotonergic system in early life: neurodevelopmental underpinnings of autism-related behavior

    NARCIS (Netherlands)

    Kinast, K.; Peeters, D.; Kolk, S.M.; Schubert, D.; Homberg, J.R.

    2013-01-01

    Serotonin, in its function as neurotransmitter, is well-known for its role in depression, autism and other neuropsychiatric disorders, however, less known as a neurodevelopmental factor. The serotonergic system is one of the earliest to develop during embryogenesis and early changes in serotonin

  15. Brain Volumes at Term-Equivalent Age in Preterm Infants : Imaging Biomarkers for Neurodevelopmental Outcome through Early School Age

    NARCIS (Netherlands)

    Keunen, Kristin; Išgum, Ivana; van Kooij, Britt J M; Anbeek, Petronella; van Haastert, Ingrid C; Koopman-Esseboom, Corine; van Stam, Petronella C; Nievelstein, Rutger A J; Viergever, Max A; de Vries, Linda S; Groenendaal, Floris; Benders, Manon J N L

    OBJECTIVE: To evaluate the relationship between brain volumes at term and neurodevelopmental outcome through early school age in preterm infants. STUDY DESIGN: One hundred twelve preterm infants (born mean gestational age 28.6 ± 1.7 weeks) were studied prospectively with magnetic resonance imaging

  16. The Validity of the Bayley-III and DDST-II in Preterm Infants With Neurodevelopmental Impairment: A Pilot Study.

    Science.gov (United States)

    Jeong, Seong Uk; Kim, Ghi Chan; Jeong, Ho Joong; Kim, Dong Kyu; Hong, Yoo Rha; Kim, Hui Dong; Park, Seok Gyo; Sim, Young-Joo

    2017-10-01

    To identify the usefulness of both the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) and Denver Developmental Screening Test II (DDST-II) in preterm babies with neurodevelopmental impairment, considering the detection rate as regulation of criteria. Retrospective medical chart reviews which included the Bayley-III and DDST-II, were conducted for 69 preterm babies. Detection rate of neurodevelopmental impairment in preterm babies were investigated by modulating scaled score of the Bayley-III. The detection rate of DDST-II was identified by regarding more than 1 caution as an abnormality. Then detection rates of each corrected age group were verified using conventional criteria. When applying conventional criteria, 22 infants and 35 infants were detected as preterm babies with neurodevelopmental impairment, as per the Bayley-III and DDST-II evaluation, respectively. Detection rates increased by applying abnormal criteria that specified as less than 11 points in the Bayley-III scaled score. In DDST-II, detection rates rose from 50% to 68.6% using modified criteria. The detection rates were highest when performed after 12 months corrected age, being 100% in DDST II. The detection rate also increased when applying the modified criteria in both the Bayley-III and DDST-II. Accurate neurologic examination is more important for detection of preterm babies with neurodevelopmental impairment. We suggest further studies for the accurate modification of the detection criteria in DDST-II and the Bayley-III for preterm babies.

  17. Differences between the family-centered "COPCA" program and traditional infant physical therapy based on neurodevelopmental treatment principles.

    Science.gov (United States)

    Dirks, Tineke; Blauw-Hospers, Cornill H; Hulshof, Lily J; Hadders-Algra, Mijna

    2011-09-01

    Evidence for effectiveness of pediatric physical therapy in infants at high risk for developmental motor disorders is limited. Therefore, "Coping With and Caring for Infants With Special Needs" (COPCA), a family-centered, early intervention program, was developed. The COPCA program is based on 2 components: (1) family involvement and educational parenting and (2) the neuromotor principles of the neuronal group selection theory. The COPCA coach uses principles of coaching to encourage the family's own capacities for solving problems of daily care and incorporating variation, along with trial and error in daily activities. The purpose of this study was to evaluate whether the content of sessions of the home-based, early intervention COPCA program differs from that of traditional infant physical therapy (TIP) sessions, which in the Netherlands are largely based on neurodevelopmental treatment. The study was conducted at the University Medical Center Groningen in the Netherlands. A quantitative video analysis of therapy sessions was conducted with infants participating in a 2-arm randomized trial. Forty-six infants at high risk for developmental motor disorders were randomly assigned to receive COPCA (n=21) or TIP (n=25) between 3 and 6 months corrected age. Intervention sessions were videotaped at 4 and 6 months corrected age and analyzed with a standardized observation protocol for the classification of physical therapy actions. Outcome parameters were relative amounts of time spent on specific physical therapy actions. The content of COPCA and TIP differed substantially. For instance, in TIP sessions, more time was spent on facilitation techniques, including handling, than in COPCA sessions (29% versus 3%, respectively). During COPCA, more time was spent on family coaching and education than during TIP (16% versus 4%, respectively). The major limitation of the study was its restriction to the Netherlands, implying that findings cannot be generalized automatically to

  18. Choline status and neurodevelopmental outcomes at 5 years of age in the Seychelles Child Development Nutrition Study

    Science.gov (United States)

    Strain, J. J.; McSorley, Emeir M.; van Wijngaarden, Edwin; Kobrosly, Roni W.; Bonham, Maxine P.; Mulhern, Maria S.; McAfee, Alison J.; Davidson, Philip W.; Shamlaye, Conrad F.; Henderson, Juliette; Watson, Gene E.; Thurston, Sally W.; Wallace, Julie M. W.; Ueland, Per M.; Myers, Gary J.

    2013-01-01

    Choline is an essential nutrient that is found in many food sources and plays a critical role in the development of the central nervous system. Animal studies have shown that choline status pre- and postnatally can have long-lasting effects on attention and memory; however, effects in human subjects have not been well studied. The aim of the present study was to examine the association between plasma concentrations of free choline and its related metabolites in children and their neurodevelopment in the Seychelles Child Development Nutrition Study, an ongoing longitudinal study assessing the development of children born to mothers with high fish consumption during pregnancy. Plasma concentrations of free choline, betaine, dimethylglycine (DMG), methionine and homocysteine and specific measures of neurodevelopment were measured in 210 children aged 5 years. The children’s plasma free choline concentration (9·17 (sd 2·09) µmol/l) was moderately, but significantly, correlated with betaine (r 0·24; P=0·0006), DMG (r 0·15; P=0·03), methionine (r 0·24; P=0·0005) and homocysteine (r 0·19; P=0·006) concentrations. Adjusted multiple linear regression revealed that betaine concentrations were positively associated with Preschool Language Scale – total language scores (β = 0·066; P=0·04), but no other associations were evident. We found no indication that free choline concentration or its metabolites, within the normal physiological range, are associated with neurodevelopmental outcomes in children at 5 years of age. As there is considerable animal evidence suggesting that choline status during development is associated with cognitive outcome, the issue deserves further study in other cohorts. PMID:23298754

  19. Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU

    DEFF Research Database (Denmark)

    Depienne, Christel; Nava, Caroline; Keren, Boris

    2017-01-01

    features of this syndrome remains uncertain. Among those, three genes, AKT3, HNRNPU and ZBTB18 are highly expressed in the brain and point mutations in these genes have been recently identified in children with neurodevelopmental phenotypes. In this study, we report the clinical and molecular data from 17...... patients with 1q43q44 microdeletions, four with ZBTB18 mutations and seven with HNRNPU mutations, and review additional data from 37 previously published patients with 1q43q44 microdeletions. We compare clinical data of patients with 1q43q44 microdeletions with those of patients with point mutations....... ZBTB18 deletions or mutations are associated with variable corpus callosum anomalies with an incomplete penetrance. ZBTB18 may also contribute to microcephaly and HNRNPU to thin corpus callosum, but with a lower penetrance. Co-deletion of contiguous genes has additive effects. Our results confirm...

  20. Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy.

    LENUS (Irish Health Repository)

    Nadeem, Montasser

    2012-01-31

    BACKGROUND: To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. METHODS: Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg\\/dL (2.6 mmol\\/L)] and hyperglycaemia [> 150 mg\\/dL (8.3 mmol\\/L)] were correlated to neurodevelopmental outcome at 24 months of age. RESULTS: Four fifths of the 468 blood samples were in the normoglycaemic range (392\\/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11\\/39) and a third of the hyperglycaemic samples (32.4%:12\\/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol\\/L and 5.02(2.35) mmol\\/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. CONCLUSION: During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome.

  1. Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

    LENUS (Irish Health Repository)

    Nadeem, Montasser

    2011-02-04

    Abstract Background To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. Methods Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg\\/dL (2.6 mmol\\/L)] and hyperglycaemia [> 150 mg\\/dL (8.3 mmol\\/L)] were correlated to neurodevelopmental outcome at 24 months of age. Results Four fifths of the 468 blood samples were in the normoglycaemic range (392\\/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11\\/39) and a third of the hyperglycaemic samples (32.4%:12\\/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol\\/L and 5.02(2.35) mmol\\/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. Conclusion During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome.

  2. Abnormal neurodevelopmental outcomes are common in children with transient congenital hyperinsulinism

    Directory of Open Access Journals (Sweden)

    Bindu Hima Avatapalle

    2013-05-01

    Full Text Available Introduction: Neuroglycopaenia is recognised to be associated with abnormal neurodevelopmental outcomes in 26-44% of children with persistent congenital hyperinsulinism (P-CHI. The prevalence of abnormal neurodevelopment in transient CHI (T-CHI is not known. We have aimed to investigate abnormal neurodevelopment and associated factors in T-CHI and P-CHI. Materials and Methods: A cohort of children with CHI (n=67, age 2.5-5 years was assessed at follow up review and noted to have normal or abnormal (mild or severe neurodevelopmental outcomes for the domains of speech and language, motor and vision. Children were classified as P-CHI (n=33, if they had undergone surgery or remained on medical therapy, or T-CHI (n=34, if medical treatment for hypoglycaemia was stopped. Results: Overall, abnormal neurodevelopment was present in 26 (39% children with CHI, of whom 18 (69% were severe. Importantly, the incidence of abnormal neurodevelopment in T-CHI was similar to that in P-CHI (30% v 47% respectively, p=0.16. The prevalence of severe abnormal neurodevelopment in speech, motor and vision domains was similar in both T-CHI and P-CHI children. For this cohort, we found that the severity of disease (based upon maximal diazoxide dose, [odds ratio (95% confidence intervals 1.3 (1.1;1.5, p=0.03] and early presentation of CHI <7 days following birth [5.9 (1.3;27.8, p=0.02] were significantly associated with abnormal neurodevelopment. There was no significant association with gender, genotype or the histopathological basis of CHI. Conclusions: Abnormal neurodevelopment was evident in one third of children with both T-CHI and P-CHI, early presentation and severe CHI being risk factors. Early recognition and rapid correction of hypoglycaemia are advocated to avoid abnormal neurodevelopment in children with CHI.

  3. Learning Disabilities in Extremely Low Birth Weight Children and Neurodevelopmental Profiles at Preschool Age.

    Science.gov (United States)

    Squarza, Chiara; Picciolini, Odoardo; Gardon, Laura; Giannì, Maria L; Murru, Alessandra; Gangi, Silvana; Cortinovis, Ivan; Milani, Silvano; Mosca, Fabio

    2016-01-01

    At school age extremely low birth weight (ELBW) and extremely low gestational age (ELGAN) children are more likely to show Learning Disabilities (LDs) and difficulties in emotional regulation. The aim of this study was to investigate the incidence of LDs at school age and to detect neurodevelopmental indicators of risk for LDs at preschool ages in a cohort of ELBW/ELGAN children with broadly average intelligence. All consecutively newborns 2001-2006 admitted to the same Institution entered the study. Inclusion criteria were BW learning disabilities at school age was investigated through a parent-report questionnaire at children's age range 9-10 years. Neurodevelopmental profiles were assessed through the Griffiths Mental Development Scales at 1 and 2 years of corrected age and at 3, 4, 5, and 6 years of chronological age and were analyzed comparing two groups of children: those with LDs and those without. At school age 24 on 102 (23.5%) of our ELBW/ELGAN children met criteria for LDs in one or more areas, with 70.8% comorbidity with emotional/attention difficulties. Children with LDs scored significantly lower in the Griffiths Locomotor and Language subscales at 2 years of corrected age and in the Personal-social, Performance and Practical Reasoning subscales at 5 years of chronological age. Our findings suggest that, among the early developmental indicators of adverse school outcome, there is a poor motor experimentation, language delay, and personal-social immaturity. Cognitive rigidity and poor ability to manage practical situations also affect academic attainment. Timely detection of these early indicators of risk is crucial to assist the transition to school.

  4. An epigenetic framework for neurodevelopmental disorders: from pathogenesis to potential therapy.

    Science.gov (United States)

    Millan, Mark J

    2013-05-01

    Neurodevelopmental disorders (NDDs) are characterized by aberrant and delayed early-life development of the brain, leading to deficits in language, cognition, motor behaviour and other functional domains, often accompanied by somatic symptoms. Environmental factors like perinatal infection, malnutrition and trauma can increase the risk of the heterogeneous, multifactorial and polygenic disorders, autism and schizophrenia. Conversely, discrete genetic anomalies are involved in Down, Rett and Fragile X syndromes, tuberous sclerosis and neurofibromatosis, the less familiar Phelan-McDermid, Sotos, Kleefstra, Coffin-Lowry and "ATRX" syndromes, and the disorders of imprinting, Angelman and Prader-Willi syndromes. NDDs have been termed "synaptopathies" in reference to structural and functional disturbance of synaptic plasticity, several involve abnormal Ras-Kinase signalling ("rasopathies"), and many are characterized by disrupted cerebral connectivity and an imbalance between excitatory and inhibitory transmission. However, at a different level of integration, NDDs are accompanied by aberrant "epigenetic" regulation of processes critical for normal and orderly development of the brain. Epigenetics refers to potentially-heritable (by mitosis and/or meiosis) mechanisms controlling gene expression without changes in DNA sequence. In certain NDDs, prototypical epigenetic processes of DNA methylation and covalent histone marking are impacted. Conversely, others involve anomalies in chromatin-modelling, mRNA splicing/editing, mRNA translation, ribosome biogenesis and/or the regulatory actions of small nucleolar RNAs and micro-RNAs. Since epigenetic mechanisms are modifiable, this raises the hope of novel therapy, though questions remain concerning efficacy and safety. The above issues are critically surveyed in this review, which advocates a broad-based epigenetic framework for understanding and ultimately treating a diverse assemblage of NDDs ("epigenopathies") lying at the

  5. Prenatal exposure to dental amalgam in the Seychelles Child Development Nutrition Study: associations with neurodevelopmental outcomes at 9 and 30 months.

    Science.gov (United States)

    Watson, Gene E; Evans, Katie; Thurston, Sally W; van Wijngaarden, Edwin; Wallace, Julie M W; McSorley, Emeir M; Bonham, Maxine P; Mulhern, Maria S; McAfee, Alison J; Davidson, Philip W; Shamlaye, Conrad F; Strain, J J; Love, Tanzy; Zareba, Grazyna; Myers, Gary J

    2012-12-01

    Dental amalgam is approximately 50% metallic mercury and releases mercury vapor into the oral cavity, where it is inhaled and absorbed. Maternal amalgams expose the developing fetus to mercury vapor. Mercury vapor can be toxic, but uncertainty remains whether prenatal amalgam exposure is associated with neurodevelopmental consequences in offspring. To determine if prenatal mercury vapor exposure from maternal dental amalgam is associated with adverse effects to cognition and development in children. We prospectively determined dental amalgam status in a cohort of 300 pregnant women recruited in 2001 in the Republic of Seychelles to study the risks and benefits of fish consumption. The primary exposure measure was maternal amalgam surfaces present during gestation. Maternal occlusal points were a secondary measure. Outcomes were the child's mental (MDI) and psychomotor (PDI) developmental indices of the Bayley Scales of Infant Development-II (BSID-II) administered at 9 and 30 months. Complete exposure, outcome, and covariate data were available on a subset of 242 mother-child pairs. The number of amalgam surfaces was not significantly (p>0.05) associated with either PDI or MDI scores. Similarly, secondary analysis with occlusal points showed no effect on the PDI or MDI scores for boys and girls combined. However, secondary analysis of the 9-month MDI was suggestive of an adverse association present only in girls. We found no evidence of an association between our primary exposure metric, amalgam surfaces, and neurodevelopmental endpoints. Secondary analyses using occlusal points supported these findings, but suggested the possibility of an adverse association with the MDI for girls at 9 months. Given the continued widespread use of dental amalgam, we believe additional prospective studies to clarify this issue are a priority. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Neurodevelopmental outcome of HIV-exposed but uninfected infants in the Mother and Infants Health Study, Cape Town, South Africa.

    Science.gov (United States)

    Springer, Priscilla E; Slogrove, Amy L; Laughton, Barbara; Bettinger, Julie A; Saunders, Henriëtte H; Molteno, Christopher D; Kruger, Mariana

    2018-01-01

    To compare neurodevelopmental outcomes of HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) infants in a peri-urban South African population. HEU infants living in Africa face unique biological and environmental risks, but uncertainty remains regarding their neurodevelopmental outcome. This is partly due to lack of well-matched HUU comparison groups needed to adjust for confounding factors. This was a prospective cohort study of infants enrolled at birth from a low-risk midwife obstetric facility. At 12 months of age, HEU and HUU infant growth and neurodevelopmental outcomes were compared. Growth was evaluated as WHO weight-for-age, length-for-age, weight-for-length and head-circumference-for-age Z-scores. Neurodevelopmental outcomes were evaluated using the Bayley scales of Infant Development III (BSID) and Alarm Distress Baby Scale (ADBB). Fifty-eight HEU and 38 HUU infants were evaluated at 11-14 months of age. Performance on the BSID did not differ in any of the domains between HEU and HUU infants. The cognitive, language and motor scores were within the average range (US standardised norms). Seven (12%) HEU and 1 (2.6%) HUU infant showed social withdrawal on the ADBB (P = 0.10), while 15 (26%) HEU and 4 (11%) HUU infants showed decreased vocalisation (P = 0.06). There were no growth differences. Three HEU and one HUU infant had minor neurological signs, while eight HEU and two HUU infants had macrocephaly. Although findings on the early neurodevelopmental outcome of HEU infants are reassuring, minor differences in vocalisation and on neurological examination indicate a need for reassessment at a later age. © 2017 John Wiley & Sons Ltd.

  7. A prospective investigation of neurodevelopmental risk factors for adult antisocial behavior combining official arrest records and self-reports.

    Science.gov (United States)

    Paradis, Angela D; Fitzmaurice, Garrett M; Koenen, Karestan C; Buka, Stephen L

    2015-09-01

    Neurodevelopmental deficits are postulated to play an important role in the etiology of persistent antisocial behavior (ASB). Yet it remains uncertain as to which particular deficits are most closely associated with ASB. We seek to advance this understanding using prospectively collected data from a birth cohort in which multiple indices of neurodevelopmental functioning and ASB were assessed. Participants (n = 2776) were members of the Providence, Rhode Island cohort of the Collaborative Perinatal Project. Information on demographic and neurodevelopmental variables was collected from pregnancy through age 7. When all offspring had reached 33 years of age an adult criminal record check was conducted. A subset of subjects also self-reported on their engagement in serious ASB. Bivariate logistic regression was used to examine the relationship between each neurodevelopmental factor and adult ASB and test whether associations varied depending on how ASB was ascertained. After controlling for background and contextual characteristics, maternal smoking during pregnancy, lower childhood verbal and performance IQ, and age 7 aggressive/impulsive behavior all significantly increased the odds of adult ASB. Associations were not modified by sex and did not depend on how ASB was assessed. However, while both males and Black participants were more likely to engage in ASB than their respective female and White counterparts, relationships were significantly stronger for official records than for self-reports. Results point to a particular subset of early neurodevelopmental risks for antisocial outcomes in adulthood. Findings also suggest that prior contradictory results are not due to the use of official records versus self-reported outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. What trial participants need to be told about placebo effects to give informed consent: a survey to establish existing knowledge among patients with back pain.

    Science.gov (United States)

    Hughes, John; Greville-Harris, Maddy; Graham, Cynthia A; Lewith, George; White, Peter; Bishop, Felicity L

    2017-12-01

    Patients require an accurate knowledge about placebos and their possible effects to ensure consent for placebo-controlled clinical trials is adequately informed. However, few previous studies have explored patients' baseline (ie, pretrial recruitment) levels of understanding and knowledge about placebos. The present online survey aimed to assess knowledge about placebos among patients with a history of back pain. A 15-item questionnaire was constructed to measure knowledge about placebos. Additional questions assessed sociodemographic characteristics, duration and severity of back pain, and previous experience of receiving placebos. Participants recruited from community settings completed the study online. 210 participants completed the questionnaire. 86.7% had back pain in the past 6 months, 44.3% currently had back pain. 4.3% had received a placebo intervention as part of a clinical trial and 68.1% had previously read or heard information about placebos. Overall knowledge of placebos was high, with participants on average answering 12.07 of 15 questions about placebos correctly (SD=2.35). However, few participants correctly answered questions about the nocebo effect (31.9% correct) and the impact of the colour of a placebo pill (55.2% correct). The findings identified key gaps in knowledge about placebos. The lack of understanding of the nocebo effect in particular has implications for the informed consent of trial participants. Research ethics committees and investigators should prioritise amending informed consent procedures to incorporate the fact that participants in the placebo arm might experience adverse side effects. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Identifying Impacts of Hydropower Regulation on Salmonid Habitats to Guide River Restoration for Existing Schemes and Mitigate Adverse Effects of Future Developments

    Science.gov (United States)

    Buddendorf, B.; Geris, J.; Malcolm, I.; Wilkinson, M.; Soulsby, C.

    2015-12-01

    A decrease in longitudinal connectivity in riverine ecosystems resulting from the construction of transverse barriers has been identified as a major threat to biodiversity. For example, Atlantic Salmon (Salmo salar) have a seasonal variety of hydraulic habitat requirements for their different life stages. However, hydropower impoundments impact the spatial and temporal connectivity of natural habitat along many salmon rivers in ways that are not fully understood. Yet, these changes may affect the sustainability of habitat at local and regional scales and so ultimately the conservation of the species. Research is therefore needed both to aid the restoration and management of rivers impacted by previous hydropower development and guide new schemes to mitigate potentially adverse effects. To this end we assessed the effects of hydropower development on the flow related habitat conditions for different salmon life stages in Scottish rivers at different spatial scales. We used GIS techniques to map the changes in structural connectivity at regional scales, applying a weighting for habitat quality. Next, we used hydrological models to simulate past and present hydrologic conditions that in turn drive reach-scale hydraulic models to assess the impacts of regulation on habitat suitability in both space and time. Preliminary results indicate that: 1) impacts on connectivity depend on the location of the barrier within the river network; 2) multiple smaller barriers may have a potentially lower impact than a single larger barrier; 3) there is a relationship between habitat and connectivity where losing less but more suitable habitat potentially has a disproportionally large impact; 4) the impact of flow regulation can lead to a deterioration of habitat quality, though the effects are spatially variable and the extent of the impact depends on salmon life stage. This work can form a basis for using natural processes to perform targeted and cost-effective restoration of rivers.

  10. Cockayne Syndrome B Protects Against Methamphetamine-Enhanced Oxidative DNA Damage in Murine Fetal Brain and Postnatal Neurodevelopmental Deficits

    Science.gov (United States)

    McCallum, Gordon P.; Wong, Andrea W.

    2011-01-01

    Abstract Methamphetamine (METH) increases the oxidative DNA lesion 8-oxoguanine (8-oxoG) in fetal mouse brain, and causes postnatal motor coordination deficits after in utero exposure. Like oxoguanine glycosylase 1 (OGG1), the Cockayne syndrome B (CSB) protein is involved in the repair of oxidatively damaged DNA, although its function is unclear. Here we used CSB-deficient Csbm/m knockout mice to investigate the developmental role of DNA oxidation and CSB in METH-initiated neurodevelopmental deficits. METH (40 mg/kg intraperitoneally) administration to pregnant Csb females on gestational day 17 increased 8-oxoG levels in Csbm/m fetal brains (p < 0.05). CSB modulated 8-oxoG levels independent of OGG1 activity, as 8-oxoG incision activity in fetal nuclear extracts was identical in Csbm/m and Csb+/+mice. This CSB effect was evident despite 7.1-fold higher OGG1 activity in Csb+/+ mice compared to outbred CD-1 mice. Female Csbm/m offspring exposed in utero to METH exhibited motor coordination deficits postnatally (p < 0.05). In utero METH exposure did not cause dopaminergic nerve terminal degeneration, in contrast to adult exposures. This is the first evidence that CSB protects the fetus from xenobiotic-enhanced DNA oxidation and postnatal functional deficits, suggesting that oxidatively damaged DNA is developmentally pathogenic, and that fetal CSB activity may modulate the risk of reactive oxygen species-mediated adverse developmental outcomes. Antioxid. Redox Signal. 14, 747–756. PMID:20673160

  11. Increasing Cumulative Exposure to Volatile Anesthetic Agents Is Associated with Poorer Neurodevelopmental Outcomes in Children with Hypoplastic Left Heart Syndrome

    Science.gov (United States)

    Diaz, Laura K.; Gaynor, J. William; Koh, Shannon J.; Ittenbach, Richard F.; Gerdes, Marsha; Bernbaum, Judy C.; Zackai, Elaine H.; Clancy, Robert R.; Rehman, Mohamed A.; Pennington, Jeffrey W.; Burnham, Nancy; Spray, Thomas L.; Nicolson, Susan C.

    2017-01-01

    Objectives Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies have identified patient factors, such as prematurity and genetic syndromes, to be associated with worse ND outcomes. However, no consistent relationships have been identified among modifiable management factors, including cardiopulmonary bypass strategies, and ND outcomes after cardiac surgery in infancy. Studies in immature animals, including primates, have demonstrated neurodegeneration and apoptosis in the brain after certain levels and extended durations of anesthetic exposure. Retrospective human studies have also suggested relationships between adverse ND effects and anesthetic exposure. Methods Cumulative minimum alveolar concentration hours (MAC-hrs) of exposure to volatile anesthetic agents (VAA) (desflurane, halothane, isoflurane and sevoflurane) were collected from an anesthetic database and medical record review for 96 patients with HLHS or variants. ND testing was performed between ages 4 and 5 years including full-scale IQ, verbal IQ, performance IQ and processing speed. Four generalized linear modes were hypothesized a priori and tested using a Gaussian (normal) distribution with an identity link. Results Cumulative VAA exposure ranged from 0 to 35.3 MAC-hrs (median 7.5 hrs). Using specified covariates identified previously as significant predictors of ND outcomes, statistically significant relationships were identified between total MAC-hrs exposure and worse full-scale IQ and verbal IQ scores (p’s < 0.05) alone and after adjusting for relevant covariates. Conclusion Increased cumulative MAC-hrs exposure to VAA is associated with worse ND outcomes in certain domains in children with HLHS and variants. PMID:27183886

  12. Neurodevelopmental implications of the use of sedation and analgesia in neonates.

    Science.gov (United States)

    Davidson, Andrew; Flick, Randall P

    2013-09-01

    Laboratory studies have shown that general anesthetics may cause accelerated apoptosis and other adverse morphologic changes in neurons of the developing brain. The mechanism may be related to the neuronal quiescence or inactivity associated with anesthetic exposure. Few data exist on how brief anesthetic exposure may affect neurodevelopment in the newborn. Good evidence however shows that untreated pain and stress have an adverse effect on neurodevelopment, and therefore, at this stage, providing effective analgesia, sedation, and anesthesia would seem to be more important than concern over neurotoxicity. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. EFFECTS OF STEEL PLANTS WITH THREE-PHASE INDUCTION FURNACES ON POWER DISTRIBUTION QUALITY OF THE EXISTING 33 kV NETWORK IN NIGERIA

    Directory of Open Access Journals (Sweden)

    Saheed Lekan Gbadamosi

    2015-08-01

    Full Text Available This study aimed at evaluating and analyzing the voltage and current distortions on the introduction of a steel production plant in a typical 33 kV distribution system in Nigeria, with a view to assisting decisions made in the present system operation and planning effective service delivery in terms of quality. A three phase induction furnace was developed using MatLab Simulink software and the effects of steel plant loads on the quality of electric power system supply to electricity users on the same distribution network was analyzed in terms of total harmonic distortions of voltage and current. In order to evaluate voltage magnitude profile on the network, load flow computation and analyses were carried out on the 33 kV distribution network before and after the introduction of steel plant loads, using Successive Approximation Method. The results showed critical voltage magnitude profile below -5% of nominal voltage at the receiving end nodes. With the aid of the Matlab Simulink model, inadmissible voltage and current distortions of 15.47% and 10.35% were measured. Passive filter was proposed, designed and simulated, in order to mitigate these distortions caused by the steel production plant loads. By simulation, the installation of the designed passive filter gave a reduction of the distortions to permissible values. Further, for every 1 MW load increment when the steel plant is connected, network losses increased by 94%; however, for every of Mvar of filter capacity, loss reduction in the network is 5.1 MW.

  14. Effect of existence of cracks in concrete on depth of chloride penetration; Concrete no hibiware ga enbun shinto fukasa ni oyobosu eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Iyoda, T.; Uomoto, T. [The University of Tokyo, Tokyo (Japan). Institute of Industrial Science

    1998-10-01

    The results are reported of chloride penetration tests conducted for concrete without cracks and concrete with cracks for the examination of the effect of cracks on the depth of chloride penetration. It is reported that two types of concrete specimens of water/cement ratios of 50% and 70%, respectively, are prepared with reinforcement bars embedded therein, that they are subjected to bending load tests for crack initiation, and that they are next subjected to chloride penetration tests under conditions where the air temperature is 20degC, the water temperature is 20{+-}3degC, and the chloride concentration level is approximately 3%. It is stated that, as the result of the tests, it is found that the crack-free part of a specimen with cracks is roughly equal to a specimen without cracks in terms of the depth of chloride penetration, irrespective of the water/cement ratios, and that the depth of chloride penetration is in proportion approximately to the square root of the length of time of immersion in salt water. It is pointed out that the effect of cracks on the depth of chloride penetration in the cracked part of a specimen is related to the depth of cracks, but not dependent on the width of cracks on the specimen surface. 4 refs., 9 figs.

  15. Association between maternal vitamin D status in pregnancy and neurodevelopmental outcomes in childhood: results from the Avon Longitudinal Study of Parents and Children (ALSPAC).

    Science.gov (United States)

    Darling, Andrea L; Rayman, Margaret P; Steer, Colin D; Golding, Jean; Lanham-New, Susan A; Bath, Sarah C

    2017-06-01

    Seafood intake in pregnancy has been positively associated with childhood cognitive outcomes which could potentially relate to the high vitamin D content of oily fish. However, whether higher maternal vitamin D status (serum 25-hydroxyvitamin D (25(OH)D)) in pregnancy is associated with a reduced risk of offspring suboptimal neurodevelopmental outcomes is unclear. A total of 7065 mother-child pairs were studied from the Avon Longitudinal Study of Parents and Children cohort who had data for both serum total 25(OH)D concentration in pregnancy and at least one measure of offspring neurodevelopment (pre-school development at 6-42 months; 'Strengths and Difficulties Questionnaire' scores at 7 years; intelligence quotient (IQ) at 8 years; reading ability at 9 years). After adjustment for confounders, children of vitamin D-deficient mothers (<50·0 nmol/l) were more likely to have scores in the lowest quartile for gross-motor development at 30 months (OR 1·20; 95 % CI 1·03, 1·40), fine-motor development at 30 months (OR 1·23; 95 % CI 1·05, 1·44) and social development at 42 months (OR 1·20; 95 % CI 1·01, 1·41) than vitamin D-sufficient mothers (≥50·0 nmol/l). No associations were found with neurodevelopmental outcomes, including IQ, measured at older ages. However, our results suggest that deficient maternal vitamin D status in pregnancy may have adverse effects on some measures of motor and social development in children under 4 years. Prevention of vitamin D deficiency may be important for preventing suboptimal development in the first 4 years of life.

  16. Principles and Practices of Neurodevelopmental Assessment in Children: Lessons Learned from the Centers for Children’s Environmental Health and Disease Prevention Research

    Science.gov (United States)

    Dietrich, Kim N.; Eskenazi, Brenda; Schantz, Susan; Yolton, Kimberly; Rauh, Virginia A.; Johnson, Caroline B.; Alkon, Abbey; Canfield, Richard L.; Pessah, Isaac N.; Berman, Robert F.

    2005-01-01

    Principles and practices of pediatric neurotoxicology are reviewed here with the purpose of guiding the design and execution of the planned National Children’s Study. The developing human central nervous system is the target organ most vulnerable to environmental chemicals. An investigation of the effects of environmental exposures on child development is a complex endeavor that requires consideration of numerous critical factors pertinent to a study’s concept, design, and execution. These include the timing of neurodevelopmental assessment, matters of biologic plausibility, site, child and population factors, data quality assurance and control, the selection of appropriate domains and measures of neurobehavior, and data safety and monitoring. Here we summarize instruments for the assessment of the neonate, infant, and child that are being employed in the Centers for Children’s Environmental Health and Disease Prevention Research, sponsored by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, discuss neural and neurobiologic measures of development, and consider the promises of gene–environment studies. The vulnerability of the human central nervous system to environmental chemicals has been well established, but the contribution these exposures may make to problems such as attention deficit disorder, conduct problems, pervasive developmental disorder, or autism spectrum disorder remain uncertain. Large-scale studies such as the National Children’s Study may provide some important clues. The human neurodevelopmental phenotype will be most clearly represented in models that include environmental chemical exposures, the social milieu, and complex human genetic characteristics that we are just beginning to understand. PMID:16203260

  17. Avirulence (AVR) Gene-Based Diagnosis Complements Existing Pathogen Surveillance Tools for Effective Deployment of Resistance (R) Genes Against Rice Blast Disease.

    Science.gov (United States)

    Selisana, S M; Yanoria, M J; Quime, B; Chaipanya, C; Lu, G; Opulencia, R; Wang, G-L; Mitchell, T; Correll, J; Talbot, N J; Leung, H; Zhou, B

    2017-06-01

    Avirulence (AVR) genes in Magnaporthe oryzae, the fungal pathogen that causes the devastating rice blast disease, have been documented to be major targets subject to mutations to avoid recognition by resistance (R) genes. In this study, an AVR-gene-based diagnosis tool for determining the virulence spectrum of a rice blast pathogen population was developed and validated. A set of 77 single-spore field isolates was subjected to pathotype analysis using differential lines, each containing a single R gene, and classified into 20 virulent pathotypes, except for 4 isolates that lost pathogenicity. In all, 10 differential lines showed low frequency (95%), inferring the effectiveness of R genes present in the respective differential lines. In addition, the haplotypes of seven AVR genes were determined by polymerase chain reaction amplification and sequencing, if applicable. The calculated frequency of different AVR genes displayed significant variations in the population. AVRPiz-t and AVR-Pii were detected in 100 and 84.9% of the isolates, respectively. Five AVR genes such as AVR-Pik-D (20.5%) and AVR-Pik-E (1.4%), AVRPiz-t (2.7%), AVR-Pita (0%), AVR-Pia (0%), and AVR1-CO39 (0%) displayed low or even zero frequency. The frequency of AVR genes correlated almost perfectly with the resistance frequency of the cognate R genes in differential lines, except for International Rice Research Institute-bred blast-resistant lines IRBLzt-T, IRBLta-K1, and IRBLkp-K60. Both genetic analysis and molecular marker validation revealed an additional R gene, most likely Pi19 or its allele, in these three differential lines. This can explain the spuriously higher resistance frequency of each target R gene based on conventional pathotyping. This study demonstrates that AVR-gene-based diagnosis provides a precise, R-gene-specific, and differential line-free assessment method that can be used for determining the virulence spectrum of a rice blast pathogen population and for predicting the

  18. Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers.

    Science.gov (United States)

    Ye, Xin Cynthia; Ng, Isaiah; Seid-Karbasi, Puya; Imam, Tuhina; Lee, Cheryl E; Chen, Shirley Yu; Herman, Adam; Sharma, Balraj; Johal, Gurinder; Gu, Bobby; Wasserman, Wyeth W

    2013-08-06

    The Portal for Families Overcoming Neurodevelopmental Disorders (PFOND) provides a structured Internet interface for the sharing of information with individuals struggling with the consequences of rare developmental disorders. Large disease-impacted communities can support fundraising organizations that disseminate Web-based information through elegant websites run by professional staff. Such quality resources for families challenged by rare disorders are infrequently produced and, when available, are often dependent upon the continued efforts of a single individual. The project endeavors to create an intuitive Web-based software system that allows a volunteer with limited technical computer skills to produce a useful rare disease website in a short time period. Such a system should provide access to emerging news and research findings, facilitate community participation, present summary information about the disorder, and allow for transient management by volunteers who are likely to change periodically. The prototype portal was implemented using the WordPress software system with both existing and customized supplementary plug-in software modules. Gamification scoring features were implemented in a module, allowing editors to measure progress. The system was installed on a Linux-based computer server, accessible across the Internet through standard Web browsers. A prototype PFOND system was implemented and tested. The prototype system features a structured organization with distinct partitions for background information, recent publications, and community discussions. The software design allows volunteer editors to create a themed website, implement a limited set of topic pages, and connect the software to dynamic RSS feeds providing information about recent news or advances. The prototype was assessed by a fraction of the disease sites developed (8 out of 27), including Aarskog-Scott syndrome, Aniridia, Adams-Oliver syndrome, Cat Eye syndrome, Kabuki syndrome

  19. Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers

    Science.gov (United States)

    Imam, Tuhina; Lee, Cheryl E; Chen, Shirley Yu; Herman, Adam; Sharma, Balraj; Johal, Gurinder; Gu, Bobby

    2013-01-01

    Background The Portal for Families Overcoming Neurodevelopmental Disorders (PFOND) provides a structured Internet interface for the sharing of information with individuals struggling with the consequences of rare developmental disorders. Large disease-impacted communities can support fundraising organizations that disseminate Web-based information through elegant websites run by professional staff. Such quality resources for families challenged by rare disorders are infrequently produced and, when available, are often dependent upon the continued efforts of a single individual. Objective The project endeavors to create an intuitive Web-based software system that allows a volunteer with limited technical computer skills to produce a useful rare disease website in a short time period. Such a system should provide access to emerging news and research findings, facilitate community participation, present summary information about the disorder, and allow for transient management by volunteers who are likely to change periodically. Methods The prototype portal was implemented using the WordPress software system with both existing and customized supplementary plug-in software modules. Gamification scoring features were implemented in a module, allowing editors to measure progress. The system was installed on a Linux-based computer server, accessible across the Internet through standard Web browsers. Results A prototype PFOND system was implemented and tested. The prototype system features a structured organization with distinct partitions for background information, recent publications, and community discussions. The software design allows volunteer editors to create a themed website, implement a limited set of topic pages, and connect the software to dynamic RSS feeds providing information about recent news or advances. The prototype was assessed by a fraction of the disease sites developed (8 out of 27), including Aarskog-Scott syndrome, Aniridia, Adams-Oliver syndrome

  20. Effects of Cannabis on the Adolescent Brain

    Science.gov (United States)

    Jacobus, Joanna; Tapert, Susan F.

    2014-01-01

    This article reviews neuroimaging, neurocognitive, and preclinical findings on the effects of cannabis on the adolescent brain. Marijuana is the second most widely used intoxicant in adolescence, and teens who engage in heavy marijuana use often show disadvantages in neurocognitive performance, macrostructural and microstructural brain development, and alterations in brain functioning. It remains unclear whether such disadvantages reflect pre-existing differences that lead to increased substances use and further changes in brain architecture and behavioral outcomes. Future work should focus on prospective investigations to help disentangle dose-dependent effects from pre-existing effects, and to better understand the interactive relationships with other commonly abused substances (e.g., alcohol) to better understand the role of regular cannabis use on neurodevelopmental trajectories. PMID:23829363

  1. Effect of co-existing ions during the preparation of alumina by electrolysis with aluminum soluble electrodes: Structure and defluoridation activity of electro-synthesized adsorbents

    Energy Technology Data Exchange (ETDEWEB)

    Tchomgui-Kamga, Eric, E-mail: etchomgui@yahoo.fr [UMR CNRS n°6226 Institut des Sciences Chimiques de Rennes, ENSCR, Avenue du Général Leclerc, CS 50837 - 35708 Rennes Cedex 7 (France); Laboratoire de Chimie Analytique, Faculté des Sciences, Université de Yaoundé-I, BP 812 Yaoundé (Cameroon); Audebrand, Nathalie, E-mail: nathalie.audebrand@univ-rennes1.fr [UMR CNRS n°6226 Institut des Sciences Chimiques de Rennes, Université de Rennes-1, Avenue du Général Leclerc, 35042 Rennes Cedex (France); Darchen, André, E-mail: Andre.Darchen@ensc-rennes.fr [UMR CNRS n°6226 Institut des Sciences Chimiques de Rennes, ENSCR, Avenue du Général Leclerc, CS 50837 - 35708 Rennes Cedex 7 (France)

    2013-06-15

    Highlights: • pH increases during electrocoagulation with aluminum electrodes are rationalized. •Composition of electrogenerated aluminas is dependent upon the electrolyte used. • All the electrogenerated aluminas contained nanoparticles of boehmite AlOOH. • The defluoridation activity of the aluminas was dependent upon the electrolyte used. -- Abstract: The electrochemical dissolution of aluminum was carried out to prepare hydrated aluminas which were characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), chemical titrations and defluoridation activities. Aluminas were obtained at controlled pH depending upon the counter cations of the electrolyte. A boehmite AlOOH phase was isolated mainly in ammonium solution, while aluminas synthesized in the other media contained a mixture of phases, usually both boehmite and bayerite γ-Al(OH){sub 3}. All the boehmite phases contained nano-crystallites of less than 3 nm. Batch defluoridation experiments revealed a second influence of the original electrolyte. Aluminas were very effective in defluoridation with abatement rates of 99.5%, 98.5% and 97.3% from neutral fluoride solution at 10 mg L{sup −1} when they were prepared in solution of (NH{sub 4}){sub 2}SO{sub 4}, (NH{sub 4})HCO{sub 2} and NH{sub 4}Cl, respectively. The maximum fluoride capacities were 46.94; 10.25 and 12.18 mg g{sup −1} for aluminas prepared in solution of (NH{sub 4}){sub 2}SO{sub 4}; (NH{sub 4})HCO{sub 2} and NH{sub 4}Cl, respectively. The amount of dissolved Al was found to be less than 0.19 mg L{sup −1} at neutral pH. These results show that a defluoridation with electro-synthesized aluminas would be more efficient and safe than a direct electrocoagulation.

  2. Audible and infrasonic noise levels in the cabins of modern agricultural tractors — Does the risk of adverse, exposure-dependent effects still exist?

    Directory of Open Access Journals (Sweden)

    Bartosz Bilski

    2013-06-01

    Full Text Available Introduction: The agricultural tractor is one of the most commonly used vehicles on farms and one of the most prominent sources of noise. This article presents an exemplary assessment of the audible and infrasonic noise levels in the cabins of selected modern wheeled agricultural tractors. Materials and Methods: Operator-perceived audible and infrasonic noise levels in the cabins were examined for 20 types of modern tractors during typical conditions of work. The tractors had been in use for no longer than 3 years, with rated power between 96 kW and 227 kW, designed and produced by world-renowned companies. Noise level measurements were performed in accordance with PN-EN ISO 9612:2011 (ISO 9612:2009. Results: Audible noise levels (A-weighted ranged from 62.1 to 87.4 dB-A (average: 68.2 to 83.8 dB-A for different work tasks. The factors influencing noise levels include performed tasks, soil, weather conditions and the skills of individual drivers. In spectrum analysis, the highest noise levels occurred at frequencies 250 Hz, 1 and 2 kHz. Infrasound noise levels (G-weighted ranged from 87.3 to 111.3 dB-G. The driver-experienced exposure to infrasound was found to increase significantly when the vehicle was in motion. Conclusions: Average audible noise levels have no potential to adversely affect the hearing organ during tasks performed inside the closed cabins of the analysed modern agricultural tractors. Due to the relatively low audible noise levels inside the cabins of modern agricultural tractors, non-auditory effects are the only adverse symptoms that can develop. Modern agricultural tractors emit considerable infrasonic noise levels. All tractors introduced into the market should be subjected to tests with regard to infrasonic noise levels.

  3. Linagliptin provides effective, well-tolerated add-on therapy to pre-existing oral antidiabetic therapy over 1 year in Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Inagaki, N; Watada, H; Murai, M; Kagimura, T; Gong, Y; Patel, S; Woerle, H-J

    2013-09-01

    To evaluate the long-term safety and efficacy of linagliptin as add-on therapy to one approved oral antidiabetic drug (OAD) in Japanese patients with type 2 diabetes mellitus and insufficient glycaemic control. This 52-week, multicentre, open-label, parallel-group study evaluated once-daily linagliptin 5 mg as add-on therapy to one OAD [biguanide, glinide, glitazone, sulphonylurea (SU) or α-glucosidase inhibitors (A-GI)] in 618 patients. After a 2-week run-in, patients on SU or A-GI were randomized to either linagliptin (once daily, 5 mg) or metformin (twice or thrice daily, up to 2250 mg/day) as add-on therapy. Patients receiving the other OADs received linagliptin add-on therapy (non-randomized). Adverse events were mostly mild or moderate, and rates were similar across all groups. Hypoglycaemic events were rare, except in the SU group. Overall, 26 (5.8%) hypoglycaemic events were reported in patients receiving linagliptin (non-randomized). Hypoglycaemic events were similar for linagliptin and metformin added to A-GI (1/61 vs. 2/61, respectively) or SU (17/124 vs. 10/63, respectively). Significant reductions in glycated haemoglobin (HbA1c) levels (between -0.7 and -0.9%) occurred throughout the study period for the background therapy groups that received linagliptin (baseline HbA1c 7.9-8.1%). The decline in HbA1c levels was indistinguishable between linagliptin and metformin groups when administered as add-on therapy to A-GI or SU. Once-daily linagliptin showed safety and tolerability over 1 year and provided effective add-on therapy leading to significant HbA1c reductions, similar to metformin, over 52 weeks in Japanese patients. © 2013 Blackwell Publishing Ltd.

  4. Development and analysis of the factor structure of parents' internalized stigma of neurodevelopmental disorder in child scale

    Directory of Open Access Journals (Sweden)

    Ananya Mahapatra

    2017-01-01

    Full Text Available Background: Parents of children suffering from neurodevelopmental disorders, frequently face public stigma which is often internalized and leads to psychological burden. However, there is a lack of data on the perceptions of internalized stigma among parents of children with neurodevelopmental disorders, especially from lower-middle-income countries like India. Aims: This study aims to develop an adapted version of the Internalized Stigma of Mental Illness (ISMI scale for use in parents of children suffering from neurodevelopmental disorders and to explore the factor structure of this instrument through exploratory factor analysis (EFA. Settings and Design: A cross-sectional study was conducted in an outpatient setting in a tertiary care hospital in India. Materials and Methods: A total of 105 parents of children suffering from neurodevelopmental disorders (according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition were recruited for the study after screening for psychiatric disorder using Mini International Neuropsychiatric Interview version 6.0. A modified 16-item scale was constructed Parents' Internalized Stigma of Neurodevelopmental Disorder in Child (PISNC scale and applied on 105 parents of children suffering from neurodevelopmental disorders, after translation to Hindi and back-translation, in keeping with the World Health Organization's translation-back-translation methodology. Statistical Analysis: EFA was carried out using principal component analysis with orthogonal (varimax rotation. Internal consistency of the Hindi version of the scale was estimated in the form of Cronbach's alpha. Spearman–Brown coefficient and Guttman split-half coefficient were calculated to evaluate the split-half reliability. Results: The initial factor analysis yielded three-factor models with an eigenvalue of >1 and the total variance explained by these factors was 62.017%. The internal consistency of the 16-item scale was 0

  5. Step-Initiation Deficits in Children with Faulty Posture Diagnosed with Neurodevelopmental Disorders during Infancy

    Directory of Open Access Journals (Sweden)

    Magdalena Stania

    2017-11-01

    Full Text Available BackgroundEarly detection of movement deficits during step initiation will facilitate the selection of the optimal physiotherapy management strategy. The main aim of the study was to assess potential differences in step initiation between 5- and 6-year-old children with faulty posture who had been diagnosed with neurodevelopmental disorders during infancy and healthy children.MethodsThe experimental group consisted of 19 children aged 5–6 years with faulty posture, who had been diagnosed with neurodevelopmental disorders during infancy and were given physiotherapy in the first year of their lives. The control group comprised 19 nursery school children aged 5–6 years with no postural defects, no history of postural control or movement deficits, and no physiotherapy interventions in the first year of their lives. Step initiation was performed on force platforms under various conditions, i.e., with and without an obstacle, stepping up onto a platform placed at a higher level, stepping down onto a platform placed on a lower level. The recording of center of foot pressure (COP displacements was divided into three phases: phase 1 (P1—quiet standing before step initiation, phase 2 (P2—transit, phase 3 (P3—quiet standing until measurement completion.ResultsThe Tukey post hoc test showed that the means of sway range (raCOP and mean velocity (vCOP in sagittal (AP plane for phase 1 and vCOP in frontal (ML plane for phase 3 registered in the step-up trial were significantly higher (p < 0.05 in children with faulty posture compared to children with typical development. P1vCOPML, P3vCOPAP, P3raCOPML, and P3vCOPMLof the step-down trial were also significantly higher in children with faulty posture (p < 0.05.ConclusionInclusion of functional movement exercises (stair-walking tasks in physiotherapy interventions for children with postural defects seems well justified.The trial was registered in the Australian and New Zealand Clinical Trials

  6. Neurodevelopmental and behavioral outcome of very low birth weight babies at corrected age of 2 years.

    Science.gov (United States)

    Mukhopadhyay, Kanya; Malhi, Prahbhjot; Mahajan, Rama; Narang, Anil

    2010-09-01

    Neurodevelopmental and behavioral assessment of very low birth weight babies (VLBW) at corrected age (CA) of 2 years. 127, 110, 99 and 101 babies ≤34 weeks and ≤1500 g were followed at CA of 3, 6, 9, 12 months respectively for developmental and neurological assessment. DASII (Developmental assessment scale for Indian infants) was used at CA of 18 months and preschool behavioural checklist (PBCL) at CA 2 years. Of 101 VLBW babies available for follow up at CA 1 year, 3 (3%) babies had Cerebral Palsy (CP) and 3% (n = 3) had suspect abnormality (mild hypotonia), 11% (n = 11) had gross motor and 8% (n = 8) had language abnormality. Their mean mental (MeDQ) and motor (MoDQ) quotients were 80.4 ± 10.7 and 77.2 ± 13.3 and a score of < 70 was found in 17% (MeDQ) and 25.7% (MoDQ) VLBW babies. High PBCL score (mean 16.8 ± 5.4) was seen in 84%VLBW babies. On subgroup analysis, 2 babies (5%) in subgroup1 ( n = 54, ≤1200 g,) and 1 (1.6%) in subgroup 2 (n = 78, 1201-1500 g) had CP. Twelve (29%) in subgroup 1 had significant language delay (p = 0.004) as compared to 4 (15%) in subgroup 2 at 1 year. BSID and PBCL scores were comparable. Amongst ELBW babies (<1000 g), 6.6% (n = 1) had CP, 25% (n = 3) and 42% (n = 5) had low MeDQ and MoDQ respectively and all of them had high PBCL score. AGA and SGA had similar outcome. VLBW babies need close and longer follow up due to high risk of neurodevelopmental and behavioral abnormality.

  7. Psychosocial functioning in children with neurodevelopmental disorders and externalizing behavior problems.

    Science.gov (United States)

    Arim, Rubab G; Kohen, Dafna E; Garner, Rochelle E; Lach, Lucyna M; Brehaut, Jamie C; MacKenzie, Michael J; Rosenbaum, Peter L

    2015-01-01

    This study examines psychosocial functioning in children with neurodevelopmental disorders (NDDs) and/or externalizing behavior problems (EBPs) as compared to children with neither condition. The longitudinal sample, drawn from the Canadian National Longitudinal Survey of Children and Youth, included children who were 6 to 9 years old in Cycle 1 who were followed-up biennially in Cycles 2 and 3 (N = 3476). The associations between NDDs and/or EBPs, child and family socio-demographic characteristics and parenting behaviors (consistency and ineffective parenting), were examined across several measures of child psychosocial functioning: peer relationships, general self-esteem, prosocial behavior and anxiety-emotional problems. Children with NDDs, EBPs, and both NDDs and EBPs self-reported lower scores on general self-esteem. Children with NDDs and both NDDs and EBPs reported lower scores on peer relationships and prosocial behavior. Lastly, children with both NDDs and EBPs self-reported higher scores on anxiety-emotional behaviors. After considering family socio-demographic characteristics and parenting behaviors, these differences remained statistically significant only for children with both NDDs and EBPs. Child age and gender, household income and parenting behaviors were important in explaining these associations. Psychosocial functioning differs for children with NDDs and/or EBPs. Children with both NDDs and EBPs appear to report poorer psychosocial functioning compared to their peers with neither condition. However, it is important to consider the context of socio-demographic characteristics, parenting behaviors and their interactions to understand differences in children's psychosocial functioning. Implication for Rehabilitation: Practitioners may wish to consider complexity in child health by examining a comprehensive set of determinants of psychosocial outcomes as well as comorbid conditions, such as neurodevelopmental disorders (NDDs) and externalizing

  8. Long-term neurodevelopmental outcomes of infants born late preterm: a systematic review

    Directory of Open Access Journals (Sweden)

    Tripathi T

    2015-11-01

    Full Text Available Tanya Tripathi,1 Stacey C Dusing2,3 1Rehabilitation and Movement Science Program, Department of Physical Therapy, 2Department of Physical Therapy, 3Department of Pediatrics, Children's Hospital of Richmond, Virginia Commonwealth University, Richmond, VA, USA Purpose: Late preterm (LPT births constitute a large proportion of the preterm births in the USA. Over the last few decades, there has been an increase in research focusing on the neurodevelopment of infants born LPT. The purpose of this research was to systematically review the long-term neurodevelopmental outcomes in LPT infants. Materials and methods: We identified studies by using PubMed, ERIC, CINAHL, and PsycINFO databases. The references of included papers were reviewed for additional papers that met the inclusion criteria. Included papers compared motor, cognitive, language development, or academic performance outcomes between individuals born LPT and a term control group assessed between 12 months and 18 years of age. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards for systematic reviews were utilized including a two-step, two-investigator review process. Results: Of the 4,720 studies found in the initial search, 20 studies met the inclusion criteria. Approximately 75% of the 16 studies that assessed cognitive outcomes reported cognitive delay in the LPT group when compared to their full-term counterparts. More than 50% of the seven studies that assessed motor outcomes suggested a delay in motor development in the LPT group in comparison to full-term. Fewer papers assessed academic performance and language in children born LPT; however, the majority identified borderline differences when LPT infants were compared to those born full-term. Conclusion: Evidence suggests that infants born LPT are at an increased risk of neurodevelopmental delay between 1 and 18 years of life when compared to those born at term. The delay is most evident in the cognitive

  9. Prediction of neurodevelopmental and sensory outcome at 5 years in Norwegian children born extremely preterm.

    Science.gov (United States)

    Leversen, Katrine Tyborg; Sommerfelt, Kristian; Rønnestad, Arild; Kaaresen, Per Ivar; Farstad, Theresa; Skranes, Janne; Støen, Ragnhild; Bircow Elgen, Irene; Rettedal, Siren; Egil Eide, Geir; Irgens, Lorentz M; Markestad, Trond

    2011-03-01

    To examine the prevalence of neurodevelopmental disability and the predictive value of pre-, peri-, and postnatal data on neurologic, sensory, cognitive, and motor function in children born extremely preterm. This was a prospective observational study of all infants born in Norway between 1999 and 2000 with gestational ages between 22 and 27 weeks or birth weights between 500 and 999 g. Cognitive function was assessed with the Wechsler Preschool and Primary Scale of Intelligence-Revised, motor function with the Movement Assessment Battery for Children, and severity of cerebral palsy with the Gross Motor Function Classification for Cerebral Palsy. Disabilities were described as mild, moderate, or severe. Of 371 eligible children, 306 (82%) were examined at a mean (SD) age of 5 years and 10 (4) months. For gestational age less than 28 weeks (n = 239), 26 (11%) children had cerebral palsy alone (n = 21) or in combination with blindness (n = 3) or deafness (n = 2); 1 was blind and 1 was deaf. Of the remaining children, the mean full-scale IQ was 94 ± 15, and significant predictors were (values given as the difference in IQ points [95% confidence intervals]) high maternal education (9.6 [5.7-13.4]), preeclampsia (-7.7 [-12.7 to -2.7]), and retinopathy of prematurity higher than grade 2 (-17.5 [-27.1 to -8.0]). Movement Assessment Battery for Children scores were positively associated with gestational age and prenatal steroids and negatively associated with being small for gestational age, male gender, and having retinopathy of prematurity. Moderate to severe neurodevelopmental disability was more common for gestational ages 25 weeks or less (28 of 87 children) than for 26 to 27 weeks (12 of 152 children; P children; P = .001). The outcome was poorer for children with gestational ages of 25 weeks or less compared with those with gestational ages between 26 and 27 weeks. For those without cerebral palsy, blindness, or deafness, however, gestational age had a limited

  10. Existing Steel Railway Bridges Evaluation

    Directory of Open Access Journals (Sweden)

    Vičan Josef

    2016-12-01

    Full Text Available The article describes general principles and basis of evaluation of existing railway bridges based on the concept of load-carrying capacity determination. Compared to the design of a new bridge, the modified reliability level for existing bridges evaluation should be considered due to implementation of the additional data related to bridge condition and behaviour obtained from regular inspections. Based on those data respecting the bridge remaining lifetime, a modification of partial safety factors for actions and materials could be respected in the bridge evaluation process. A great attention is also paid to the specific problems of determination of load-caring capacity of steel railway bridges in service. Recommendation for global analysis and methodology for existing steel bridge superstructure load-carrying capacity determination are described too.

  11. High efficient removal of molybdenum from water by Fe{sub 2}(SO{sub 4}){sub 3}: Effects of pH and affecting factors in the presence of co-existing background constituents

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiang; Ma, Jun, E-mail: majunhit@126.com; Lu, Xixin; Huangfu, Xiaoliu; Zou, Jing

    2015-12-30

    Highlights: • Proposed high efficient Mo (VI) removal with Fe{sub 2}(SO{sub 4}){sub 3} coagulation-filtration. • Studied different effects of Fe{sub 2}(SO{sub 4}){sub 3} and FeCl{sub 3} due to different anionic portions. • Reported the adverse effect of calcium on the removal of Mo (VI). • Proposed factors affecting Mo (VI) removal: intercepted Fe and adsorption affinity. - Abstract: Comparatively investigated the different effects of Fe{sub 2}(SO{sub 4}){sub 3} coagulation-filtration and FeCl{sub 3} coagulation-filtration on the removal of Mo (VI). And the influence of calcium, sulfate, silicate, phosphate and humic acid (HA) were also studied. The following conclusions can be obtained: (1) compared with the case of FeCl{sub 3}, Fe{sub 2}(SO{sub 4}){sub 3} showed a higher Mo (VI) removal efficiency at pH 4.00–5.00, but an equal removal efficiency at pH 6.00–9.00. (2) The optimum Mo (VI) removal by Fe{sub 2}(SO{sub 4}){sub 3} was achieved at pH 5.00–6.00; (3) The presence of calcium can reduce the removal of Mo (VI) over the entire pH range in the present study; (4) The effect of co-existing background anions (including HA) was dominated by three factors: Firstly the influence of co-existing background anions on the content of Fe intercepted from water (intercepted Fe). Secondly the competition of co-existing anions with Mo (VI) for adsorption sites. Thirdly the influence of co-existing background anions on the Zeta potential of the iron flocs.

  12. Insulin-Like Growth Factor 1 and Related Compounds in the Treatment of Childhood-Onset Neurodevelopmental Disorders

    Directory of Open Access Journals (Sweden)

    Cyrus Vahdatpour

    2016-09-01

    Full Text Available Insulin-Like Growth Factor 1 (IGF-1 is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD, both recombinant IGF-1 (mecasermin and related derivatives, such as (1-3 IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome. In broader ASD, clinical trials are ongoing. Here, we review the role of IGF-1 in the molecular etiologies of these conditions in addition to the accumulating evidence from early clinical studies highlighting the possibility of IGF-1 and related compounds as potential treatments for these childhood-onset neurodevelopmental disorders.

  13. Existence of mesons after deconfinement

    NARCIS (Netherlands)

    F. Brau (Fabian); F. Buisseret

    2007-01-01

    textabstractWe investigate the possibility for a quark-antiquark pair to form a bound state at temperatures higher than the critical one ($T>T_c$), thus after deconfinement. Our main goal is to find analytical criteria constraining the existence of such mesons. Our formalism relies on a Schrödinger

  14. Limitations of existing web services

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Limitations of existing web services. Uploading or downloading large data. Serving too many user from single source. Difficult to provide computer intensive job. Depend on internet and its bandwidth. Security of data in transition. Maintain confidentiality of data ...

  15. Performance of Existing Hydrogen Stations

    Energy Technology Data Exchange (ETDEWEB)

    Sprik, Samuel [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kurtz, Jennifer M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ainscough, Christopher D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Saur, Genevieve [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Peters, Michael C [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-12-01

    In this presentation, the National Renewable Energy Laboratory presented aggregated analysis results on the performance of existing hydrogen stations, including performance, operation, utilization, maintenance, safety, hydrogen quality, and cost. The U.S. Department of Energy funds technology validation work at NREL through its National Fuel Cell Technology Evaluation Center (NFCTEC).

  16. PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.

    Science.gov (United States)

    Zollo, Massimo; Ahmed, Mustafa; Ferrucci, Veronica; Salpietro, Vincenzo; Asadzadeh, Fatemeh; Carotenuto, Marianeve; Maroofian, Reza; Al-Amri, Ahmed; Singh, Royana; Scognamiglio, Iolanda; Mojarrad, Majid; Musella, Luca; Duilio, Angela; Di Somma, Angela; Karaca, Ender; Rajab, Anna; Al-Khayat, Aisha; Mohan Mohapatra, Tribhuvan; Eslahi, Atieh; Ashrafzadeh, Farah; Rawlins, Lettie E; Prasad, Rajniti; Gupta, Rashmi; Kumari, Preeti; Srivastava, Mona; Cozzolino, Flora; Kumar Rai, Sunil; Monti, Maria; Harlalka, Gaurav V; Simpson, Michael A; Rich, Philip; Al-Salmi, Fatema; Patton, Michael A; Chioza, Barry A; Efthymiou, Stephanie; Granata, Francesca; Di Rosa, Gabriella; Wiethoff, Sarah; Borgione, Eugenia; Scuderi, Carmela; Mankad, Kshitij; Hanna, Michael G; Pucci, Piero; Houlden, Henry; Lupski, James R; Crosby, Andrew H; Baple, Emma L

    2017-04-01

    PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  17. Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders.

    Science.gov (United States)

    Gabriel, Elke; Gopalakrishnan, Jay

    2017-04-14

    The restricted availability of suitable in vitro models that can reliably represent complex human brain development is a significant bottleneck that limits the translation of basic brain research into clinical application. While induced pluripotent stem cells (iPSCs) have replaced the ethically questionable human embryonic stem cells, iPSC-based neuronal differentiation studies remain descriptive at the cellular level but fail to adequately provide the details that could be derived from a complex, 3D human brain tissue. This gap is now filled through the application of iPSC-derived, 3D brain organoids, "Brains in a dish," that model many features of complex human brain development. Here, a method for generating iPSC-derived, 3D brain organoids is described. The organoids can help with modeling autosomal recessive primary microcephaly (MCPH), a rare human neurodevelopmental disorder. A widely accepted explanation for the brain malformation in MCPH is a depletion of the neural stem cell pool during the early stages of human brain development, a developmental defect that is difficult to recreate or prove in vitro. To study MCPH, we generated iPSCs from patient-derived fibroblasts carrying a mutation in the centrosomal protein CPAP. By analyzing the ventricular zone of microcephaly 3D brain organoids, we showed the premature differentiation of neural progenitors. These 3D brain organoids are a powerful in vitro system that will be instrumental in modeling congenital brain disorders induced by neurotoxic chemicals, neurotrophic viral infections, or inherited genetic mutations.

  18. Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition

    Directory of Open Access Journals (Sweden)

    Reut Gruber

    2016-01-01

    Full Text Available Empirical evidence indicates that sleep spindles facilitate neuroplasticity and “off-line” processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population.

  19. Development of comorbid crying, sleeping, feeding problems across infancy: Neurodevelopmental vulnerability and parenting.

    Science.gov (United States)

    Bilgin, Ayten; Wolke, Dieter

    2017-06-01

    Regulatory problems (excessive crying, feeding, and sleeping difficulties), specifically their comorbidity, are early warning signs of future problems. Insensitive parenting and neurodevelopmental vulnerabilities have been suggested as factors explaining development or maintenance of regulatory problems. Nevertheless, none of the previous studies investigated these factors within the same sample across infancy, taking into account the reciprocal influences between maternal sensitivity and regulatory problems. To investigate the prospective association between very preterm birth, comorbid regulatory problems and maternal sensitivity. 178 participants including 73 very preterm/very low birth weight and 105 full-term infants and their caretakers. A prospective study from birth to 18months. Regulatory problems were measured at term, 3months and 18months with a structured parental interview. Maternal sensitivity was measured with a nurse observation at term; and a researcher observation of play tasks at 3months and at 18months. Very preterm birth was associated with regulatory problems at term (β=0.19, SE=0.10, pproblems across infancy. Maternal sensitivity at term had a negative association to regulatory problems at 3months (β=-0.26, SE=0.12, pproblems in comparison to sensitive parenting. Copyright © 2017. Published by Elsevier B.V.

  20. Myelination deficit in a phencyclidine-induced neurodevelopmental model of schizophrenia.

    Science.gov (United States)

    Zhang, Ruiguo; He, Jue; Zhu, Shenghua; Zhang, Handi; Wang, Hongxing; Adilijiang, Abulimiti; Kong, Lynda; Wang, Junhui; Kong, Jiming; Tan, Qingrong; Li, Xin-Min

    2012-08-21

    Increasing evidence supports an important role of oligodendrocytes and myelination in the pathogenesis of schizophrenia. Oligodendrocytes are the myelin-producing cells in the central nervous system. To test the myelination dysfunction hypothesis of schizophrenia, possible myelination dysfunction was evaluated in a phencyclidine (PCP)-induced neurodevelopmental model of schizophrenia. On postnatal day (PND) 2, rat pups were treated with a total 14 subcutaneous daily injections of PCP (10mg/kg) or saline. PCP-injected rats showed schizophrenia-like behaviors including hyper-locomotor activity on PND 30 and prepulse inhibition deficit on PND 31. Cerebral myelination was measured by the expression of myelin basic protein (MBP), and cerebral mature oligodendrocytes were measured by the expression of glutathione S-transferase (GST)-π in rats. The results indicate that the expressions of MBP on PND 16, 22 and 32 and GST-π on PND 22 decreased in the frontal cortex of PCP-injected rats. Our results suggest that there was myelination impairment in the phencyclidine-induced schizophrenia animal model, and indicate that myelination may play an important role in the pathogenesis of schizophrenia. Copyright © 2012 Elsevier B.V. All rights reserved.