Pubmed du 03/07/19

mercredi 3 juillet 2019

1. Brunero F, Venerosi A, Chiarotti F, Arduino GM. Are touch screen technologies more effective than traditional educational methods in children with autism spectrum disorders ? A pilot study. Annali dell’Istituto superiore di sanita. 2019 ; 55(2) : 151-60.

Applied Computer technologies can address the needs of individuals with autism spectrum disorders (ASD). Data on the efficacy of assistive technology in ASD is limited, and its effectiveness in supporting and facilitating skill acquisition in this specific population must be still demonstrated. 63 Italian ASD subjects underwent learning activities administered by cardboards or a touch screen support. The support preference was evaluated in a choice trial, and quantitative analysis was performed on items regarding communication and challenging behaviours. Touch devices are attractive especially for males without intellectual disability and a lower communication and cooperation behaviours with the use of touch screen compared with paper support was shown depending on activities. Overall, our data do not confirm the hypothesis that touch screen presentation improves activity completion and behavioural performance for each individual with ASD. Data discourage an indiscriminate use of these devices and suggest analysing with more attention the core ingredients that should shape digital devices when used for people on ASD.

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2. Bruno JL, Hosseini SH, Lightbody AA, Manchanda MK, Reiss AL. Brain circuitry, behavior, and cognition : A randomized placebo-controlled trial of donepezil in fragile X syndrome. Journal of psychopharmacology (Oxford, England). 2019 : 269881119858304.

BACKGROUND : Fragile X syndrome, the most common inherited cause for intellectual disability, is associated with alterations in cholinergic among other neurotransmitter systems. This study investigated the effects of donepezil hydrochloride, a cholinesterase inhibitor that has potential to correct aberrant cholinergic signaling. METHOD : Forty-two individuals with fragile X syndrome (mean age=19.61 years) were randomized to receive 2.5-10.0 mg of donepezil (n=20, seven females) or placebo (n=22, eight females) per day. One individual in the active group withdrew at week 7. Outcomes included the contingency naming test, the aberrant behavior checklist, and behavior and brain activation patterns during a functional magnetic resonance imaging gaze discrimination task. RESULTS : There were no significant differences between active and placebo groups on cognitive (contingency naming task) or behavioral (total score or subscales of the aberrant behavior checklist) outcomes. At baseline, the active and placebo groups did not differ in functional magnetic resonance imaging activation patterns during the gaze task. After 12 weeks of treatment the active group displayed reduced activation in response to the averted vs direct gaze contrast, relative to the placebo group, in the left superior frontal gyrus. CONCLUSIONS : Reduced functional brain activation for the active group may represent less arousal in response to direct eye gaze, relative to the placebo group. Change in functional magnetic resonance imaging activation patterns may serve as a more sensitive metric and predictor of response to treatment when compared to cognitive and behavioral assessments. Our results suggest that donepezil may have an impact on brain functioning, but longer term follow-up and concomitant behavioral intervention may be required to demonstrate improvement in cognition and behavior.

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3. Fries BE, James ML, Martin L, Head MJ, Park PS. A Case-Mix System for Adults with Developmental Disabilities. Health services insights. 2019 ; 12 : 1178632919856011.

Effective management of publicly funded services matches the provision of needed services with cost-efficient payment methods. Payment systems that recognize differences in care needs (eg, case-mix systems) allow for greater proportions of available funds to be directed to providers supporting individuals with more needs. We describe a new way to allocate funds spent on adults with intellectual disabilities (ID) as part of a system-wide Medicaid payment reform initiative in Arkansas. Analyses were based on population-level data for persons living at home, collected using the interRAI ID assessment system, which were linked to paid service claims. We used automatic interactions detection to sort individuals into unique groups and provide a standardized relative measure of the cost of the services provided to each group. The final case-mix system has 33 distinct final groups and explains 26% of the variance in costs, which is similar to other systems in health and social services sectors. The results indicate that this system could be the foundation for a future case-mix approach to reimbursement and stand the test of "fairness" when examined by stakeholders, including parents, advocates, providers, and political entities.

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4. Ghodsi R, Kheirouri S. Positive association between plasma levels of advanced glycation and precursor of lipoxidation end products with gastrointestinal problems in children with autism. Current pediatric reviews. 2019.

BACKGROUND : Increased oxidative stress has been reported in autistic patients. Besides, evidence linking oxidative stress to enhancement of advanced glycation and lipoxidation end products (AGEs and ALEs) and their precursors. OBJECTIVE : This study was aimed to compare the plasma levels of the AGEs and precursors of ALEs in autistic and healthy children and to evaluate their relation with autism comorbidities. METHODS : In this cross-sectional study, 54 children, 36 autistic and 18 healthy, participated. Plasma levels of AGEs and precursors of ALEs were measured by ELISA method. Severity of autism and GI disorders were measured by GARSII questionnaire and QPGS-ROMEIII questionnaire, respectively. RESULTS : Plasma levels of AGEs and precursors of ALEs in autistic children was comparable with healthy children. Plasma levels of AGEs and precursor of ALEs were correlated with physical activity and GI disorders in autistic children. A strong association was also found between AGEs and precursors of ALEs. CONCLUSIONS : The results indicated that AGEs and ALEs have a strong correlation together but the AGEs and precursor of ALEs in autistic children are not different from healthy children.

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5. Guan K, Lau AS, Zhang A, Chlebowski C, Haine-Schlagel R, Brookman-Frazee L. In-Session Caregiver Behaviors during Evidence-Based Intervention Delivery for Children with ASD in Community Mental Health Services. Evidence-based practice in child and adolescent mental health. 2019 ; 4(1) : 55-71.

An Individualized Mental Health Intervention for ASD, ("AIM HI"), is a collaborative, caregiver-mediated and child-directed intervention for reducing challenging behaviors in children with autism spectrum disorder developed for delivery in community mental health programs. Using observational data from AIM HI sessions, the present study characterized the occurrence of two types of in-session caregiver behaviors : expressed concerns (i.e., expressing concerns about treatment strategies ; expressing difficulty using skills ; expressing difficulty completing homework) and participation engagement (i.e., asking questions ; participating in session activities ; showing commitment to therapy). Further analyses examined cultural differences in caregiver behaviors and associations between caregiver behaviors and clinician adherence. Participants included 39 caregiver-clinician dyads enrolled in a community effectiveness trial of AIM HI. Video recordings from 107 sessions during the first two months of treatment were coded for in-session caregiver behaviors and clinician adherence. Results indicated that expressed concerns were observed in 47% of sessions. When controlling for household income, Latinx caregivers were rated lower for expressing concerns about treatment strategies and demonstrated lower participation engagement behaviors in session compared with non-Latinx White caregivers, suggesting that cultural factors may impact verbal engagement in sessions. Finally, expressing concerns about treatment strategies, expressing difficulty using skills, and participation engagement were positively associated with clinician adherence. Findings suggest that some expressed concerns and participation engagement behaviors may be indicators of positive caregiver engagement in the context of a collaborative intervention, and lower levels of such caregiver engagement may actually impede clinicians’ delivery of intensive evidence-based intervention in routine care.

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6. Gubbiotti M, Balboni G, Bini V, Elisei S, Bedetti C, Marchiafava M, Giannantoni A. Bladder and bowel dysfunction, adaptive behaviour and psychiatric profiles in adults affected by autism spectrum disorders. Neurourology and urodynamics. 2019.

AIMS : Bladder and bowel dysfunction (BBD) have been recognized in children affected by autism spectrum disorder (ASD), but no consistent information exist in adults with the condition. We evaluated the prevalence of BBD and the impact of psychiatric and behavioural profiles in adults affected by ASD. METHODS : Twenty-two adults and 13 children/teens with ASD and a matched group of typically developing subjects (TD) were prospectively studied. Patients and TD subjects underwent the evaluation of urinary incontinence (UI : diurnal, continuous or intermittent), nocturnal enuresis (NE), and bowel disturbances with the 3-day voiding and bowel diary. In addition, assessment of intellectual disability (ID) and psychiatric and adaptive behaviours with the Neuropsychiatric Inventory Scale (NPI) and the Vineland Adaptive Behaviour Scale 2nd Edition (Vineland-II), was performed. RESULTS : In adults, any type of incontinence was observed in 81.8% of cases, and NE and intermittent UI in 59.0% and 36.3% of patients, respectively. Faecal incontinence and constipation were detected 36.3% and in 68.1% of cases, respectively. ID was severe in 2 cases and profound in 18 ; NPI and Vineland-II items most affected were "Irritability/Lability," "Motor Activity," and "Agitation," and IQ-Socialization and IQ-Communication. Significant relationships were identified between intermittent UI and greater ID (P < .02) and high "anxiety" (P < .05), and between NE and high "euphoria/elevated mood" (P < .05). These results were similar to those observed in children/teens. CONCLUSIONS : Adults with ASD, and greater ID and mood disorders, present with a high prevalence of BBD. A shared pathogenetic mechanism could underlie the co-occurrence of ASD, mood disorders, and BBD.

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7. Gulle ZN, Karayagmurlu A, Coskun M. Raynaud’s Phenomenon Related with Atomoxetine Treatment in a Child with Autism and Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2019.

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8. Guma E, Plitman E, Chakravarty MM. The role of maternal immune activation in altering the neurodevelopmental trajectories of offspring : a translational review of neuroimaging studies with implications for autism spectrum disorder and schizophrenia. Neurosci Biobehav Rev. 2019.

Exposure to maternal infection in utero increases the risk that offspring will develop neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia.Research in animal models has confirmed this link and demonstrated that maternal immune activation (MIA) is sufficient to induce alterations in offspring neurodevelopment. Building homology between observations made in humans and animal models is a challenge ; however, neuroimaging allows for homologous characterization of developmental trajectories across species.This systematic review aims to discuss findings from human and animal studies that performed neuroimaging in offspring exposed to maternal infection, inflammation, or MIA, in the context of neurodevelopmental disorders.

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9. Hessabi M, Rahbar MH, Dobrescu I, Bach MA, Kobylinska L, Bressler J, Grove ML, Loveland KA, Mihailescu I, Nedelcu MC, Moisescu MG, Matei BM, Matei CO, Rad F. Concentrations of Lead, Mercury, Arsenic, Cadmium, Manganese, and Aluminum in Blood of Romanian Children Suspected of Having Autism Spectrum Disorder. Int J Environ Res Public Health. 2019 ; 16(13).

Environmental exposure to lead (Pb), mercury (Hg), arsenic (As), cadmium (Cd), manganese (Mn), and aluminum (Al) has been associated with neurodevelopmental disorders including autism spectrum disorder (ASD). We conducted a pilot study during May 2015-May 2107 to estimate blood concentrations of six metals (Pb, Hg, As, Cd, Mn, and Al) and identify their associated factors for children with ASD or suspected of having ASD in Romania. Sixty children, age 2-8 years, were administered versions of ADOS or ADI-R translated from English to Romanian. After assessment, 2-3 mL of blood was obtained and analyzed for the concentrations of the six metals. The mean age of children was 51.9 months and about 90% were male. More than half (65%) of the children were born in Bucharest. Over 90% of concentrations of As and Cd were below limits of detection. Geometric mean concentrations of Pb, Mn, Al, and Hg were 1.14 mug/dL, 10.84 mug/L, 14.44 mug/L, and 0.35 mug/L, respectively. Multivariable linear regression analysis revealed that children who were female, had less educated parents, exhibited pica, and ate cold breakfast (e.g., cereal), watermelon, and lamb had significantly higher concentrations of Pb compared to their respective referent categories (all p < 0.05 except for eating lamb, which was marginally significant, p = 0.053). Although this is the first study that provides data on concentrations of the six metals for Romanian children with ASD, the findings from this study could be useful for designing future epidemiologic studies for investigating the role of these six metals in ASD in Romanian children.

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10. Humble J, Hiratsuka K, Kasai H, Toyoizumi T. Intrinsic Spine Dynamics Are Critical for Recurrent Network Learning in Models With and Without Autism Spectrum Disorder. Frontiers in computational neuroscience. 2019 ; 13 : 38.

It is often assumed that Hebbian synaptic plasticity forms a cell assembly, a mutually interacting group of neurons that encodes memory. However, in recurrently connected networks with pure Hebbian plasticity, cell assemblies typically diverge or fade under ongoing changes of synaptic strength. Previously assumed mechanisms that stabilize cell assemblies do not robustly reproduce the experimentally reported unimodal and long-tailed distribution of synaptic strengths. Here, we show that augmenting Hebbian plasticity with experimentally observed intrinsic spine dynamics can stabilize cell assemblies and reproduce the distribution of synaptic strengths. Moreover, we posit that strong intrinsic spine dynamics impair learning performance. Our theory explains how excessively strong spine dynamics, experimentally observed in several animal models of autism spectrum disorder, impair learning associations in the brain.

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11. Kurochkin I, Khrameeva E, Tkachev A, Stepanova V, Vanyushkina A, Stekolshchikova E, Li Q, Zubkov D, Shichkova P, Halene T, Willmitzer L, Giavalisco P, Akbarian S, Khaitovich P. Metabolome signature of autism in the human prefrontal cortex. Communications biology. 2019 ; 2 : 234.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with yet incompletely uncovered molecular determinants. Alterations in the abundance of low molecular weight compounds (metabolites) in ASD could add to our understanding of the disease. Indeed, such alterations take place in the urine, plasma and cerebellum of ASD individuals. In this work, we investigated mass-spectrometric signal intensities of 1,366 metabolites in the prefrontal cortex grey matter of 32 ASD and 40 control individuals. 15% of these metabolites showed significantly different intensities in ASD and clustered in 16 metabolic pathways. Of them, ten pathways were altered in urine and blood of ASD individuals (Fisher test, p < 0.05), opening an opportunity for the design of new diagnostic instruments. Furthermore, metabolic measurements conducted in 40 chimpanzees and 40 macaques showed an excess of metabolite intensity differences unique to humans, supporting the hypothesized disruption of evolutionary novel cortical mechanisms in ASD.

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12. Li H, Leung MT. Relations between verb factivity and first-order and second-order false belief understanding : Evidence from Mandarin-speaking typically developing children and children with autism spectrum disorders. Clinical linguistics & phonetics. 2019 : 1-16.

Previous studies have shown that factivity is closely related to first-order false belief (FB). However, whether the role of factivity in first-order FB extends to second-order FB remains unclear. Investigations of verb factivity and second-order FB would contribute to our knowledge of the role of language in theory of mind (ToM) development. This study examined relations between verb factivity and first-order and second-order FB reasoning in 156 four- to seven-year-old typically developing (TD) Mandarin-speaking children, and in 17 children with autism spectrum disorders (ASD) and 17 TD matched controls. Children’s understanding of a factive zhidao ’know’, a non-factive juede ’think’ and a counter-factive jiazhuang ’pretend’ was assessed by a truth value judgement task. For TD children, zhidao ’know’ (factive) significantly predicted their first-order and second-order FB performances, and jiazhuang ’pretend’ (counter-factive) significantly predicted their first-order FB performance. For autistic children, they performed significantly poorer than their TD counterparts on complementation, verb factivity, first-order and second-order FB, and their first-order FB performance was significantly related to jiazhuang ’pretend’ (counter-factive). The findings suggest that verb factivity relates to both first-order and second-order FB, and verbs differing in factuality and mental state status contribute differently to ToM development.

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13. Nystrom P, Thorup E, Bolte S, Falck-Ytter T. Joint Attention in Infancy and the Emergence of Autism. Biol Psychiatry. 2019.

BACKGROUND : In typical infant development, parents and their children jointly contribute to establishing frequent episodes of joint attention that boost language acquisition and shape social cognition. Here we used novel live eye-tracking technology to evaluate the degree to which autism spectrum disorder (ASD) is related to reduced responding to others’ joint attention bids in infancy (RJA) and to a reduced tendency to initiate joint attention episodes (IJA). Because young infants use their gaze for both RJA and IJA, this approach allowed us to quantify these elusive processes early in life. METHODS : The final sample consisted of 112 infants (54 boys and 58 girls), of whom 81 were at familial risk for ASD and 31 were typically developing low-risk infants. At follow-up (36 months of age), 22 children in the high-risk group were diagnosed with ASD. RESULTS : At 10 months of age, rates of IJA were lower in infants later diagnosed with ASD than in the comparison groups (effect sizes d = 0.78-0.95) and followed an atypical developmental trajectory from 10 to 18 months (p < .002). RJA distinguished infants based on familial ASD risk, albeit not ASD diagnosis. The differences in IJA could not be explained by overall looking time, social preference, eye movement latencies, or number of fixations. CONCLUSIONS : This live eye-tracking study suggests that during an important period for the development of social cognition (10-18 months of age), infants later diagnosed with ASD show marked atypicalities in IJA but not in RJA. The results indicate that IJA is an important target for future prodromal intervention trials.

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14. Pagani M, Bertero A, Liska A, Galbusera A, Sabbioni M, Barsotti N, Colenbier N, Marinazzo D, Scattoni ML, Pasqualetti M, Gozzi A. Deletion of Autism Risk Gene Shank3 Disrupts Prefrontal Connectivity. J Neurosci. 2019 ; 39(27) : 5299-310.

Mutations in the synaptic scaffolding protein SHANK3 are a major cause of autism and are associated with prominent intellectual and language deficits. However, the neural mechanisms whereby SHANK3 deficiency affects higher-order socio-communicative functions remain unclear. Using high-resolution functional and structural MRI in adult male mice, here we show that loss of Shank3 (Shank3B (-/-)) results in disrupted local and long-range prefrontal and frontostriatal functional connectivity. We document that prefrontal hypoconnectivity is associated with reduced short-range cortical projections density, and reduced gray matter volume. Finally, we show that prefrontal disconnectivity is predictive of social communication deficits, as assessed with ultrasound vocalization recordings. Collectively, our results reveal a critical role of SHANK3 in the development of prefrontal anatomy and function, and suggest that SHANK3 deficiency may predispose to intellectual disability and socio-communicative impairments via dysregulation of higher-order cortical connectivity.SIGNIFICANCE STATEMENT Mutations in the synaptic scaffolding protein SHANK3 are commonly associated with autism, intellectual, and language deficits. Previous research has linked SHANK3 deficiency to basal ganglia dysfunction, motor stereotypies, and social deficits. However, the neural mechanism whereby Shank3 gene mutations affects cortical functional connectivity and higher-order socio-communicative functions remain unclear. Here we show that loss of SHANK3 in mice results in largely disrupted functional connectivity and abnormal gray matter anatomy in prefrontal areas. We also show that prefrontal connectivity disruption is tightly linked to socio-communicative deficits. Our findings suggest that SHANK3 is a critical orchestrator of frontocortical function, and that disrupted connectivity of prefrontal areas may underpin socio-communicative impairments observed in SHANK3 mutation carriers.

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15. Provenzani U, Fusar-Poli L, Brondino N, Damiani S, Vercesi M, Meyer N, Rocchetti M, Politi P. What are we targeting when we treat autism spectrum disorder ? A systematic review of 406 clinical trials. Autism. 2019 : 1362361319854641.

The number of trials aimed at evaluating treatments for autism spectrum disorder has been increasing progressively. However, it is not clear which outcome measures should be used to assess their efficacy, especially for treatments which target core symptoms. The present review aimed to provide a comprehensive overview regarding the outcome measures used in clinical trials for people with autism spectrum disorder. We systematically searched the Web of Knowledge(SM) database between 1980 and 2016 to identify published controlled trials investigating the efficacy of interventions in autism spectrum disorder. We included 406 trials in the final database, from which a total of 327 outcome measures were identified. Only seven scales were used in more than 5% of the studies, among which only three measured core symptoms (Autism Diagnostic Observation Schedule, Childhood Autism Rating Scale, and Social Responsiveness Scale). Of note, 69% of the tools were used in the literature only once. Our systematic review has shown that the evaluation of efficacy in intervention trials for autism spectrum disorder relies on heterogeneous and often non-specific tools for this condition. The fragmentation of tools may significantly hamper the comparisons between studies and thus the discovery of effective treatments for autism spectrum disorder. Greater consensus regarding the choice of these measures should be reached.

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16. Rotharmel M, Moulier V, Vasse M, Isaac C, Faerber M, Bendib B, Mirea-Grivel I, Opolczynski G, Rosier A, Guillin O. A Prospective Open-Label Pilot Study of Transcranial Direct Current Stimulation in High-Functioning Autistic Patients with a Dysexecutive Syndrome. Neuropsychobiology. 2019 : 1-11.

BACKGROUND : Executive functions (EF) are often impaired in autism spectrum disorder (ASD). Such dysfunctions are associated with anxiety, depression, and a lack of autonomy. Transcranial direct current stimulation (tDCS) has been shown to enhance EF in healthy adults and clinical populations and to improve working memory - a component of the EF - in adults with high-functioning ASD (HF-ASD). We hypothesized that tDCS could improve the EF of HF-ASD patients. Such enhancement could improve their adaptive behaviors. METHOD : Eight patients with HF-ASD received 10 consecutive cathodal tDCS sessions (2 mA) over the left dorsolateral prefrontal cortex (F3) for 15 min each in an open trial. EF (with the Stroop test, Trail Making Test [TMT] A and B, Modified Wisconsin Card Sorting Test [mWCST], and Verbal Fluency Test) and behavioral dysexecutive syndrome (with the Behavioral Dysexecutive Syndrome Inventory and the Repetitive and Restricted Behaviour scale) were assessed before and 10 days after treatment. RESULTS : This study showed significant improvement in initiation (TMT-A time : p = 0.018) and cognitive flexibility (TMT-B time : p = 0.009 ; letter Verbal Fluency Test : p = 0.017 ; mWCST total errors : p = 0.028) after tDCS. Regarding behavior, the hypoactivity of the patients improved, as well as their repetitive and restrictive behaviors. In addition, this noninvasive neurostimulation technique was well tolerated. CONCLUSIONS : Flexibility and initiation are the most impaired EF in autism. These are promising results which justify a randomized and placebo-controlled study in a wider population. If these results were confirmed by a randomized controlled trial, tDCS could be an easy and well-tolerated adjunctive treatment aiming to improve the quality of life and the autonomy of ASD patients.

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17. Selvapandiyan J. Improvising Pragmatic Cognitive-Behavioral Therapy for Depressed Adolescents With Asperger Syndrome. The primary care companion for CNS disorders. 2019 ; 21(3).

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18. Spassiani NA, Meisner BA, Abou Chacra MS, Heller T, Hammel J. What is and isn’t working : Factors involved in sustaining community-based health and participation initiatives for people ageing with intellectual and developmental disabilities. J Appl Res Intellect Disabil. 2019.

As people with intellectual and developmental disabilities (I/DD) age, it is important that I/DD agencies are prepared to support healthy ageing in homes and in communities. This study explored supports and barriers to sustaining community-based health and participation initiatives (CBHPI) for people ageing with I/DD living in group homes managed by agencies. The study utilized interviews and photovoice with 70 participants-35 individuals with I/DD and 35 management/direct support agency staff. Data were analysed through content analysis and triangulation of data where five themes emerged : Agency values and policies related to healthy ageing ; resources and staff competencies ; communication between management and staff ; community/university partnerships ; and peer relations. Findings show that I/DD agencies and people with I/DD value CBHPI, but they find them difficult to sustain due to limited resources and lack of training specific to ageing with I/DD. Conducting system-level research within I/DD agencies to include first-person accounts of people with I/DD, staff and management provides insight on how to effectively support the needs of people with I/DD to improve their health and community participation as they age.

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19. Verma AK, Khan E, Mishra SK, Jain N, Kumar A. Piperine Modulates Protein Mediated Toxicity in Fragile X-Associated Tremor/Ataxia Syndrome through Interacting Expanded CGG Repeat (r(CGG)(exp)) RNA. ACS chemical neuroscience. 2019.

An expansion of CGG tandem repeats in the 5’ untranslated region (5’-UTR) of fragile X mental retardation 1 ( FMR1) gene causes fragile X-associated tremor/ataxia syndrome (FXTAS). The transcripts of these expanded repeats r(CGG)(exp) either form RNA foci or undergo the repeat-associated non-ATG (RAN) translation that produces toxic homopolymeric proteins in neuronal cells. The discovery of small molecule modulators that possess a strong binding affinity and high selectivity to these toxic expanded repeats RNA could be a promising therapeutic approach to cure the expanded repeat-associated neurological diseases. Therefore, here we sought to test the therapeutic potential of a natural alkaloid, piperine, by assessing its ability to bind and neutralize the toxicity of r(CGG)(exp) RNA motif. To accomplish this first, we have determined the affinity of piperine to r(CGG)(exp) RNA using fluorescence-based binding assay and isothermal titration calorimetry assay. These assays showed that piperine forms a thermodynamically favorable interaction with r(CGG)(exp) RNA with high selectivity to the G-rich RNA motif. Interaction of piperine with r(CGG)(exp) motif was further validated using several biophysical techniques such as CD, CD melting, NMR spectroscopy, and gel retardation assay. Moreover, piperine was also found to be effective for improving the r(CGG)(exp) associated splicing defects and RAN translation in a FXTAS cell model system. Our results effectively provided the evidence that piperine strongly interacts with r(CGG)(exp) RNA and could be used as a suitable candidate for therapeutic development against FXTAS.

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