1. Amin SB, Smith T, Wang H. {{Is neonatal jaundice associated with autism spectrum disorders: a systematic review}}. {J Autism Dev Disord};2011 (Nov);41(11):1455-1463.
Using guidelines of the Meta-analysis of Observational Studies in Epidemiology Group, we systematically reviewed the literature on neonatal jaundice (unconjugated hyperbilirubinemia) and Autism Spectrum Disorder (ASD) in term and preterm infants. Thirteen studies were included in a meta-analysis. Most used retrospective matched case-control designs. There was significant heterogeneity (Q = 31, p = 0.002) and no evidence of publication bias (p = 0.12). Overall, jaundice, assessed by total serum bilirubin (TSB), was associated with ASD (OR, 1.43, 95% CI 1.22-1.67, random effect model). This association was not found in preterms (OR 0.7, 95% CI 0.38-1.02) but deserves further investigation since other measures of bilirubin such as unbound unconjugated bilirubin may be better predictors of neurotoxicity than TSB in preterms.
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2. Bernardi L, Tuzzi A. {{Analyzing Written Communication in AAC Contexts: A Statistical Perspective}}. {Augment Altern Commun};2011 (Sep);27(3):183-194.
This research note focuses on some of the opportunities provided by the statistical analysis of textual data, by illustrating examples of the use of lexicon-based quantitative measures with texts within a particular context of augmentative and alternative communication. The corpus is composed of 12 essays produced by six individuals with autism and six participants without disabilities in a control group during sessions of facilitated communication. The study raises questions that can be answered thanks to the statistical methods implemented in the text analysis framework and other procedures that may be used to identify the characteristics of texts (and their writers) and compare texts (or subcorpora). The aim is to discuss strengths, weaknesses, opportunities, and threats of the approach and to highlight its connections to qualitative approaches.
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3. Brown WT. {{Clinical aspects of the fragile x syndrome}}. {Results Probl Cell Differ};2012;54:273-279.
Fragile X syndrome patients express a wide array of cognitive and other gender-specific phenotypic features. These manifestations result not only from molecular mechanisms that are altered as a result of the expansion of a CGG-repeat region in the FMR1 promoter, but also genetic factors such as founder effects and mosaicism. In this chapter, I will summarize the many and varied features of fragile X syndrome as they present themselves in a clinical setting and describe the procedures that are used to diagnose patients. Finally, I will briefly touch on recent developments that will affect patient screening in the future.
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4. Castren M. {{Neural stem cells}}. {Results Probl Cell Differ};2012;54:33-40.
Neural stem/progenitor cell (NPC) cultures are a tool to study the differentiation of neuronal cells and can be used to model disease conditions in studies investigating the pathological mechanisms affecting the development and cellular plasticity of the central nervous system. There is evidence that abnormalities of NPCs and their differentiation contribute to the pathophysiology of fragile X syndrome. The results obtained with NPC cultures derived from human and mouse brain tissue with the fragile X mutation are in line with the abnormalities of Fmr1-knockout mouse brain in vivo indicating that NPC cultures can be useful as a model for fragile X syndrome.
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5. Channon S, Collins R, Swain E, Young MB, Fitzpatrick S. {{The Use of Skilled Strategies in Social Interactions by Groups High and Low in Self-Reported Social Skill}}. {J Autism Dev Disord};2011 (Oct 19)
Individuals high or low in self-reported social skill were recruited opportunistically. When presented with everyday social scenarios ending with an awkward request or offer, the high social skill participants more often used sophisticated strategies that showed greater consideration for all parties. By contrast, the low skill participants were more reliant on simple strategies including acquiescence or refusal, and the emotional tone of their responses was less positive. Greater reliance on sophisticated rather than simple strategies may be linked to more successful social interactions. The potential implications are considered for understanding everyday performance in skilled individuals and populations with limited social skills, such as those with autistic spectrum disorders.
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6. Denman RB. {{Vignettes: models in absentia}}. {Results Probl Cell Differ};2012;54:361-383.
In this chapter, I will concisely summarize the salient features of all of the fragile X models (ex vivo, non-mouse, mouse, novel mouse, and human) that were not able to be described by their creators in separate chapters. By doing so, it is hoped that this book will become more of an encyclopedic compendium.
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7. Denman RB. {{Introduction: reminiscing on models and modeling}}. {Results Probl Cell Differ};2012;54:1-12.
This chapter answers three basic questions, which are: (1) Why build models, (2) why build models of fragile X syndrome, and (3) what has been learned from the models of fragile X syndrome that have been made? The first question is used to frame the other two questions, providing the appropriate context by which the rest of the book should be examined. Of necessity the last two questions are only addressed briefly, and from one man’s point of view, as they contain the subject matter of the entirety of the book. Thus, the reader is introduced to the various topics under review and urged to read for him/herself their contents, drawing such conclusions as he/she thinks are warranted.
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8. Goebel-Goody SM, Lombroso PJ. {{Taking STEPs Forward to Understand Fragile X Syndrome}}. {Results Probl Cell Differ};2012;54:223-241.
A priority of fragile X syndrome (FXS) research is to determine the molecular mechanisms underlying the functional, behavioral, and structural deficits in humans and in the FXS mouse model. Given that metabotropic glutamate receptor (mGluR) long-term depression (LTD) is exaggerated in FXS mice, considerable effort has focused on proteins that regulate this form of synaptic plasticity. STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific phosphatase implicated as an « LTD protein » because it mediates AMPA receptor internalization during mGluR LTD. STEP also promotes NMDA receptor endocytosis and inactivates ERK1/2 and Fyn, thereby opposing synaptic strengthening. We hypothesized that dysregulation of STEP may contribute to the pathophysiology of FXS. We review how STEP’s expression and activity are regulated by dendritic protein synthesis, ubiquitination, proteolysis, and phosphorylation. We also discuss implications for STEP in FXS and other disorders, including Alzheimer’s disease. As highlighted here, pharmacological interventions targeting STEP may prove successful for FXS.
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9. Hagerman R, Lauterborn J, Au J, Berry-Kravis E. {{Fragile x syndrome and targeted treatment trials}}. {Results Probl Cell Differ};2012;54:297-335.
Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism.
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10. Hunsaker MR, Arque G, Berman RF, Willemsen R, Hukema RK. {{Mouse models of the fragile x premutation and the fragile x associated tremor/ataxia syndrome}}. {Results Probl Cell Differ};2012;54:255-269.
The use of mutant mouse models of neurodevelopmental and neurodegenerative disease is essential in order to understand the pathogenesis of many genetic diseases such as fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS). The choice of which animal model is most suitable to mimic a particular disease depends on a range of factors, including anatomical, physiological, and pathological similarities; presence of orthologs of genes of interest; and conservation of basic cell biological and metabolic processes. In this chapter, we will discuss two mouse models of the fragile X premutation which have been generated to study the pathogenesis of FXTAS and the effects of potential therapeutic interventions. Behavioral, molecular, neuropathological, and endocrine features of the mouse models and their relation to human FXTAS are discussed.
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11. Huot ME, Bisson N, Moss T, Khandjian EW. {{Manipulating the fragile x mental retardation proteins in the frog}}. {Results Probl Cell Differ};2012;54:165-179.
The frog is a model of choice to study gene function during early development, since a large number of eggs are easily obtained and rapidly develop external to the mother. This makes it a highly flexible model system in which direct tests of gene function can be investigated by microinjecting RNA antisense reagents. Two members of the Fragile X Related (FXR) gene family, namely xFmr1 and xFxr1 have been identified in Xenopus. While the tissue distribution of their products was found to be identical to that in mammals, the pattern of isoform expression is less complex. Translational silencing of the xFmr1 and xFxr1 mRNAs by microinjection of antisense morpholino oligonucleotides (MO) induced dramatic morphological alterations, revealing tissue-specific requirements for each protein during development and in maintaining the steady state levels of a range of transcripts in these tissues. The power and versatility of the frog model is that the MO-induced phenotypes can be rescued by microinjection of the corresponding MO-insensitive mRNAs. Most importantly, this animal model allows one rapidly to determine whether any member of the FXR family can compensate for the absence of another, an approach that cannot be performed in other animal models.
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12. Idrissi AE, Yan X, L’Amoreaux W, Brown WT, Dobkin C. {{Neuroendocrine alterations in the fragile x mouse}}. {Results Probl Cell Differ};2012;54:201-221.
The expression of GABA(A) receptors in the fragile X mouse brain is significantly downregulated. We additionally found that the expression of somatostatin and voltage-sensitive calcium channels (VSCCs) is also reduced. GABA(A) and the VSCCs, through a synergistic interaction, perform a critical role in mediating activity-dependent developmental processes. In the developing brain, GABA is excitatory and its actions are mediated through GABA(A) receptors. Subsequent to GABA-mediated depolarization, the VSCCs are activated and intracellular calcium is increased, which mediates gene transcription and other cellular events. GABAergic excitation mediated through GABA(A) receptors and the subsequent activation of the VSCCs are critically important for the establishment of neuronal connectivity within immature neuronal networks. Data from our laboratories suggest that there is a dysregulation of axonal pathfinding during development in the fragile X mouse brain and that this is likely due to a dysregulation of the synergistic interactions of GABA and VSCC. Thus, we hypothesize that the altered expression of these critical channels in the early stages of brain development leads to altered activity-dependent gene expression that may potentially lead to the developmental delay characteristic of the fragile X syndrome.
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13. Jacobs S, Cheng C, Doering LC. {{Probing astrocyte function in fragile x syndrome}}. {Results Probl Cell Differ};2012;54:15-31.
Astrocytes have been recognized as a class of cells that fill the space between neurons for more than a century. From their humble beginnings in the literature as merely space filling cells, an ever expanding list of functions in the CNS now exceeds the list of functions performed by neurons. In virtually all developmental and pathological conditions in the brain, astrocytes are involved in some capacity that directly affects neuronal function. Today we recognize that astrocytes are involved in the development and function of synaptic communication. Increasing evidence suggests that abnormal synaptic function may be a prominent contributing factor to the learning disability phenotype. With the discovery of FMRP in astrocytes, coupled with a role of astrocytes in synaptic function, research directed to glial neurobiology has never been more important. This chapter highlights the current knowledge of astrocyte function with a focus on their involvement in Fragile X syndrome.
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14. Kindler S, Kreienkamp HJ. {{The role of the postsynaptic density in the pathology of the fragile x syndrome}}. {Results Probl Cell Differ};2012;54:61-80.
The protein repertoire of excitatory synapses controls dendritic spine morphology, synaptic plasticity and higher brain functions. In brain neurons, the RNA-associated fragile X mental retardation protein (FMRP) binds in vivo to various transcripts encoding key postsynaptic components and may thereby substantially regulate the molecular composition of dendritic spines. In agreement with this notion functional loss of FMRP in patients affected by the fragile X syndrome (FXS) causes cognitive impairment. Here we address our current understanding of the functional role of individual postsynaptic proteins. We discuss how FMRP controls the abundance of select proteins at postsynaptic sites, which signaling pathways regulate the local activity of FMRP at synapses, and how altered levels of postsynaptic proteins may contribute to FXS pathology.
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15. Macdonald M, Esposito P, Ulrich D. {{The Physical Activity Patterns of Children with Autism}}. {BMC Res Notes};2011 (Oct 18);4(1):422.
ABSTRACT: BACKGROUND: Although motor deficits are gaining attention in autism research much less attention has been paid to the physical activity patterns in this group of children. The participants in this study were a group of children with autism spectrum disorder (N= 72) between the ages of 9- 18 years. This cross-sectional study explored the physical activity patterns of seventy-two children with autism spectrum disorder as they aged. FINDINGS: Results indicated significant differences between the mean time spent in moderate to vigorous physical activity and the mean time spent in sedentary activity. Older children with autism spectrum disorder are significantly more physically inactive, compared to younger children. CONCLUSIONS: Physical activity programs and interventions need to address this deficit, in physical activity. Children with autism have a similar trend in physical activity patterns compared to their peers without autism; associated benefits and future research will be discussed.
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16. McBride SM, Bell AJ, Jongens TA. {{Behavior in a Drosophila model of fragile x}}. {Results Probl Cell Differ};2012;54:83-117.
This chapter will briefly tie together a captivating string of scientific discoveries that began in the 1800s and catapulted us into the current state of the field where trials are under way in humans that have arisen directly from the discoveries made in model organisms such as Drosophila (fruit flies) and mice. The hope is that research efforts in the field of fragile X currently represent a roadmap that demonstrates the utility of identifying a mutant gene responsible for human disease, tracking down the molecular underpinnings of pathogenic phenotypes, and utilizing model organisms to identify and validate potential pharmacologic targets for testing in afflicted humans. Indeed, in fragile X this roadmap has already yielded successful trials in humans (J. Med. Genetic 46(4) 266-271; Jacquemont et al. Sci Transl Med 3(64):64ra61), although the work in studying these interventions in humans is just getting underway as the work in model organisms continues to generate new potential therapeutic targets.
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17. McConachie H, Hoole S, Le Couteur AS. {{Improving mental health transitions for young people with autism spectrum disorder}}. {Child Care Health Dev};2011 (Nov);37(6):764-766.
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18. Pinborough-Zimmerman J, Bakian AV. {{Just under 1% of adults living in the community in England are estimated to have autism spectrum disorders}}. {Evid Based Ment Health};2011 (Nov);14(4):89.
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19. Price TJ, Melemedjian OK. {{Fragile X Mental Retardation Protein (FMRP) and the Spinal Sensory System}}. {Results Probl Cell Differ};2012;54:41-59.
The purpose of this chapter is to discuss the role of the fragile X mental retardation protein (FMRP) in the spinal sensory system and the potential for use of the mouse model of fragile X syndrome to better understand some aspects of the human syndrome as well as advance knowledge in other areas of investigation, such as pain amplification, an important aspect of clinical pain disorders. We describe how the Fmr1 knockout mouse can be used to better understand the role of Fmrp in axons using cultures of sensory neurons and using manipulations to these neurons in vivo. We also discuss the established evidence for a role of Fmrp in nociceptive sensitization and how this evidence relates to an emerging role of translation control as a key process in pain amplification. Finally, we explore opportunities centered on the Fmr1 KO mouse for gaining further insight into the role of translation control in pain amplification and how this model may be used to identify novel therapeutic targets. We conclude that the study of the spinal sensory system in the Fmr1 KO mouse presents several unique prospects for gaining better insight into the human disorder and other clinical issues, such as chronic pain disorders, that affect millions of people worldwide.
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20. Qurashi A, Li X, Jin P. {{Fragile x mental retardation protein and stem cells}}. {Results Probl Cell Differ};2012;54:157-164.
Stem cells, which can self-renew and produce different cell types, are regulated by both extrinsic signals and intrinsic factors. Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by the functional loss of fragile X mental retardation protein (FMRP). FMRP is a selective RNA-binding protein that forms a messenger ribonucleoprotein (mRNP) complex that associates with polyribosomes. Recently, the role of Fmrp in stem cell biology has been explored in both Drosophila and the mouse. In this chapter, we discuss the role of FMRP in regulating the proliferation and differentiation of stem cells.
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21. Sigafoos J, Wermink H, Didden R, Green VA, Schlosser RW, O’Reilly MF, Lancioni GE. {{Effects of varying lengths of synthetic speech output on augmented requesting and natural speech production in an adolescent with klinefelter syndrome}}. {Augment Altern Commun};2011 (Sep);27(3):163-171.
Students with developmental disabilities and limited or no functional speech often use speech-generating devices. While the speech-output function of such devices is considered to have potential advantages, it is unclear whether the length of synthetic speech output influences augmented communication and natural speech production. To this end, we describe a two-phase study involving an adolescent with Klinefelter syndrome. In Phase 1, the frequency of augmented requests and natural speech were compared under three speech-output conditions (no-output, short-output, and long-output). In Phase 2, augmented requests in the long-output condition were no longer reinforced to determine if this would increase natural speech production. The presence and length of speech output did not influence the frequency of augmented requesting or natural speech production in Phase 1, but extinction of augmented requesting under the long-output condition in Phase 2 was associated with a significant increase in natural speech production under that condition, relative to the two other conditions. The implications of these findings for using speech-generating devices are discussed.
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22. Tassone F, Hagerman R. {{The fragile x-associated tremor ataxia syndrome}}. {Results Probl Cell Differ};2012;54:337-357.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder clinically characterized by intention tremor and gait ataxia, in addition to other conditions including hypothyroidism, autonomic dysfunction, hypertension, peripheral neuropathy, and cognitive decline. FXTAS affects some males (approximately 40%) and in less degree female premutation carriers (8-16%) older than 50 years with an age-dependent symptomatology and penetrance. The CGG repeat number appears to influence the severity and the age of onset of the disorder. The neuropathological hallmark of FXTAS is the presence of eosinophillic, ubiquitin-positive intranuclear inclusions in both neurons and astroglia throughout brain. FXTAS is due to RNA toxicity caused by elevated levels of CGG-expanded mRNA containing 55-200 CGG repeats, which is found in the intranuclear inclusions that sequester various proteins including ubiquitin, alphaB-crystallin, lamin A/C, hnRNP A2, myelin basic protein, and Sam68. The expression of the expanded CGG repeat FMR1 mRNA also induces a cellular stress response and leads to a disruption of the nuclear lamin A/C architecture. These alterations are observable even in early development, suggesting that the expanded-repeat mRNA triggers pathogenic mechanisms that can provide a molecular basis for the neurodevelopmental abnormalities observed in some children who are carriers of an FMR1 premutation allele. Finally, the presence of cellular dysregulation in older adults who do not present clinical features of FXTAS may suggest that additional genetic or environmental protective factors may play a role in the pathogenesis of FXTAS.
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23. Tessier CR, Broadie K. {{Molecular and genetic analysis of the Drosophila model of fragile x syndrome}}. {Results Probl Cell Differ};2012;54:119-156.
The Drosophila genome contains most genes known to be involved in heritable disease. The extraordinary genetic malleability of Drosophila, coupled to sophisticated imaging, electrophysiology, and behavioral paradigms, has paved the way for insightful mechanistic studies on the causes of developmental and neurological disease as well as many possible interventions. Here, we focus on one of the most advanced examples of Drosophila genetic disease modeling, the Drosophila model of Fragile X Syndrome, which for the past decade has provided key advances into the molecular, cellular, and behavioral defects underlying this devastating disorder. We discuss the multitude of RNAs and proteins that interact with the disease-causing FMR1 gene product, whose function is conserved from Drosophila to human. In turn, we consider FMR1 mechanistic relationships in non-neuronal tissues (germ cells and embryos), peripheral motor and sensory circuits, and central brain circuits involved in circadian clock activity and learning/memory.
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24. Tranfaglia MR. {{Fragile x syndrome: a psychiatric perspective}}. {Results Probl Cell Differ};2012;54:281-295.
Fragile X syndrome (FXS) is associated with a complex but relatively consistent psychiatric phenotype. Recent research has suggested neural substrates for the behavioral abnormalities typically seen in FXS, and enhanced treatment strategies for managing disabling psychiatric comorbidity. While disease-specific, and possibly disease-modifying, therapeutics are being developed for FXS, currently available psychiatric medications can provide significant symptomatic relief of the hyperactivity, anxiety disorders, and affective disturbances often seen in the course of FXS. However, patients with fragile X may be especially susceptible to the psychiatric side effects of these medications, requiring particular care in prescribing. Recent findings concerning disease mechanisms and treatment strategies are reviewed from the perspective of a clinical psychiatrist, in an effort to enhance conventional pharmacotherapy of FXS.
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25. Wang J, Zhou X, Xia W, Sun C, Wu L. {{Autism awareness and attitudes towards treatment in caregivers of children aged 3-6 years in Harbin, China}}. {Soc Psychiatry Psychiatr Epidemiol};2011 (Oct 19)
OBJECTIVE: To (1) estimate the proportion of people in the community who could correctly recognize autism spectrum disorders (ASD); (2) describe the attitudes towards various treatments for ASD; and (3) identify factors associated with ASD recognition. METHODS: A population-based cross-sectional survey was conducted in Harbin, China (n = 4,947). We estimated the proportions of participants who were at different levels of knowledge about ASD and of their attitudes towards mental health service use. Multivariate logistic regression modeling was used to identify factors associated with the recognition of ASD. RESULTS: Overall, 2,786 (57.8%) of the respondents could recognize the ASD. Recognition of autism depended on gender, residing areas, age and educational levels. With respect to the attitudes towards mental health service use for ASD, 4,007 respondents (84.6%) chose to visit a health organization for treatment; 2,470 (68.2%) made the choice of consulting a psychotherapist. CONCLUSIONS: There is a large room for improvement in awareness about ASD and treatment in the Chinese communities. Insufficient knowledge about ASD and inappropriate attitudes towards mental health service use may impede the efforts of early identification and intervention. Health education and promotion are needed to improve people’s knowledge about ASD and available mental health services.
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26. Watson R, Parr JR, Joyce C, May C, Le Couteur AS. {{Models of transitional care for young people with complex health needs: a scoping review}}. {Child Care Health Dev};2011 (Nov);37(6):780-791.
Background Young people with complex healthcare needs (CHNs) face the challenge of transferring from child to adult health services. This study sought to identify successful models of transitional care for young people with CHNs. Three conditions were used as exemplars: cerebral palsy, autism spectrum disorders and diabetes. Methods Scoping review: using search terms concerning transitional care, four databases were systematically searched for papers published in English between 1980 and April 2010. Additional informal search methods included recommendations from colleagues working with young people with each of the three conditions and making contact with clinical and research teams with expertise in transitional care. Inclusion and exclusion criteria were applied to define the papers selected for review. A separate review of policy documents, adolescent health and transition literature was also undertaken; 10 common summary categories for the components of high-quality services were identified. All papers were coded using a framework analysis which evaluated the data in two ways using the 10 transition categories and four elements of Normalization Process Theory that are important for successful implementation and integration of healthcare interventions. Results Nineteen papers were selected for review. A very limited literature of models of service provision was identified for young people with cerebral palsy and diabetes. No models were identified for young people with autism spectrum disorders. Furthermore most publications were either descriptions of new service provision or time-limited pilot studies with little service evaluation or consideration of key elements of effective implementation. Conclusions Despite agreement about the importance of effective transitional care, there is a paucity of evidence to inform best practice about both the process of and what constitutes effective transitional care. There is therefore an urgent need for research to evaluate current transitional care practices for young people with CHNs.
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27. Winograd C, Ceman S. {{Exploring the Zebra Finch Taeniopygia guttata as a Novel Animal Model for the Speech-Language Deficit of Fragile X Syndrome}}. {Results Probl Cell Differ};2012;54:181-197.
Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and presents with markedly atypical speech-language, likely due to impaired vocal learning. Although current models have been useful for studies of some aspects of FXS, zebra finch is the only tractable lab model for vocal learning. The neural circuits for vocal learning in the zebra finch have clear relationships to the pathways in the human brain that may be affected in FXS. Further, finch vocal learning may be quantified using software designed specifically for this purpose. Knockdown of the zebra finch FMR1 gene may ultimately enable novel tests of therapies that are modality-specific, using drugs or even social strategies, to ameliorate deficits in vocal development and function. In this chapter, we describe the utility of the zebra finch model and present a hypothesis for the role of FMRP in the developing neural circuitry for vocalization.
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28. Zupan B, Toth M. {{Fmr-1 as an offspring genetic and a maternal environmental factor in neurodevelopmental disease}}. {Results Probl Cell Differ};2012;54:243-253.
Since fragile X syndrome (FXS) is a typical X-linked mendelian disorder, the protein product associated with the disease (FMRP) is absent or reduced not only in the affected individuals but, in case of full mutation, also in their mothers. Here, by using the mouse model of the disease, we provide evidence that hyperactivity, a typical symptom of FXS, is not wholly induced by the lack of Fmrp in mice but also occurs as a result of its reduced expression in their mother. Genetically wild-type offspring of mutant mothers also had hyperactivity, albeit less pronounced than the mutant offspring. However, other features of FXS reproduced in the mouse model, such as sensory hyperreactivity and seizure susceptibility, were exclusively associated with the absence of Fmrp in the offspring. These data indicate that fmr-1, the gene encoding Fmrp, can be both an offspring genetic and a maternal environmental factor in producing a neurodevelopmental condition.
