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Journal of Autism and Developmental... Jul 2024Ensuring effective use of evidence-based practice (EBP) for autism in schools is imperative due to the significantly increasing number of autistic students receiving...
Ensuring effective use of evidence-based practice (EBP) for autism in schools is imperative due to the significantly increasing number of autistic students receiving school services each year. High-quality EBP use has proven challenging in schools. Research indicates implementation climate, or how EBP are supported, rewarded, and valued, and EBP resources are related to successful implementation. However, limited understanding of system-level contextual factors that impact EBP implementation for school-based providers makes development of appropriate implementation supports challenging. Understanding these factors is crucial for selecting and tailoring implementation strategies to support EBP scale up. In this observational study, California school-based providers (n = 1084) completed surveys related to implementation climate, leadership, autism experience and EBP implementation (use, competence, knowledge). Student outcomes included state level academic and behavioral indicators. Using an implementation science framework (Aarons et al., in Administration and Policy in Mental Health and Mental Health Services Research 38:4-23, 2011) and multilevel modeling, we examined the relationship between EBP Implementation and student outcomes and the moderation effects of provider and district level factors. Higher implementation climate predicted better EBP implementation outcomes, and proved more impactful when provider hands-on autism experience was low. Greater EBP resources predicted a higher percentage of students who met math standards only when district poverty level was high. Our findings suggested moderating effects on EBP implementation from both provider and system level factors. Implementation climate and resources may be especially key in addressing equity issues related to high poverty schools in which teachers often have less autism experience.
PubMed: 38951309
DOI: 10.1007/s10803-024-06443-x -
Progress in Neuro-psychopharmacology &... Jun 2024Infection during pregnancy is a substantial risk factor for the unborn child to develop autism or schizophrenia later in life, and is thought to be driven by maternal...
Infection during pregnancy is a substantial risk factor for the unborn child to develop autism or schizophrenia later in life, and is thought to be driven by maternal immune activation (MIA). MIA can be modelled by exposing pregnant mice to Polyinosinic: polycytidylic acid (Poly-I:C), a viral mimetic that induces an immune response and recapitulates in the offspring many neurochemical features of ASD and schizophrenia, including altered BDNF-TrkB signalling and disruptions to excitatory/inhibitory balance. Therefore, we hypothesised that a BDNF mimetic, 7,8-Dihydroxyflavone (7,8-DHF), administered prophylactically to the dam may prevent the neurobehavioural sequelae of disruptions induced by MIA. Dams were treated with 7,8-DHF in the drinking water (0.08 mg/Ml) from gestational day (GD) 9-20 and were exposed to Poly-I:C at GD17 (20 mg/kg, i.p.). Foetal brains were collected 6 h post Poly-I:C exposure for RT-qPCR analysis of BDNF, cytokine, GABAergic and glutamatergic gene targets. A second adult cohort were tested in a battery of behavioural tests relevant to schizophrenia and the prefrontal cortex and ventral hippocampus dissected for RT-qPCR analysis. Foetal brains exposed to Poly-I:C showed increased IL-6, but reduced expression of Ntrk2 and multiple GABAergic and glutamatergic markers. Anxiety-like behaviour was observed in adult offspring prenatally exposed to poly-I:C, which was accompanied by altered expression of Gria2 in the prefrontal cortex and Gria4 in the ventral hippocampus. While 7-8 DHF normalised the expression of some glutamatergic (Grm5) and GABAergic (Gabra1) genes in Poly-I:C exposed offspring, it also led to substantial alterations in offspring not exposed to Poly-I:C. Furthermore, mice exposed to 7,8-DHF prenatally showed increased pre-pulse inhibition and reduced working memory in adulthood. These data advance understanding of how 7,8-DHF and MIA prenatal exposure impacts genes critical to excitatory/inhibitory pathways and related behaviour.
PubMed: 38950841
DOI: 10.1016/j.pnpbp.2024.111078 -
Biological Psychiatry Jun 2024Exaggerated responses to sensory stimuli, a hallmark of Fragile X syndrome (FXS), contribute to anxiety and learning challenges. Sensory hypersensitivity is...
BACKGROUND
Exaggerated responses to sensory stimuli, a hallmark of Fragile X syndrome (FXS), contribute to anxiety and learning challenges. Sensory hypersensitivity is recapitulated in the Fmr1 knockout (KO) mouse model of FXS. Recent studies in Fmr1 KO mice have demonstrated differences in activity of cortical interneurons and a delayed switch in the polarity of GABA signaling during development. Previously, we reported that blocking the chloride transporter NKCC1 with the diuretic bumetanide, could rescue synaptic circuit phenotypes in primary somatosensory cortex (S1) of Fmr1 KO mice. However, it remains unknown whether bumetanide can rescue earlier circuit phenotypes or sensory hypersensitivity in Fmr1 KO mice.
METHODS
We used acute and chronic systemic administration of bumetanide in Fmr1 KO mice and performed in vivo 2-photon calcium imaging to record neuronal activity, while tracking mouse behavior with high-resolution videos.
RESULTS
We demonstrate that layer (L) 2/3 pyramidal neurons in S1 of Fmr1 KO mice show a higher frequency of synchronous events at postnatal day (P) 6 compared to wild-type controls. This was reversed by acute administration of bumetanide. Furthermore, chronic bumetanide treatment (P5-P14) restored S1 circuit differences in Fmr1 KO mice, including reduced neuronal adaptation to repetitive whisker stimulation, and ameliorated tactile defensiveness. Bumetanide treatment also rectified the reduced feedforward inhibition of L2/3 neurons in S1 and boosted the circuit participation of parvalbumin interneurons.
CONCLUSIONS
This further supports the notion that synaptic, circuit, and sensory behavioral phenotypes in Fmr1 KO can be mitigated by inhibitors of NKCC1, such as the FDA-approved diuretic bumetanide.
PubMed: 38950809
DOI: 10.1016/j.biopsych.2024.06.023 -
Seminars in Speech and Language Jun 2024Researchers implemented a short-term cascading coaching model focusing on naturalistic developmental behavioral intervention with three participant triads. Triads...
Researchers implemented a short-term cascading coaching model focusing on naturalistic developmental behavioral intervention with three participant triads. Triads consisted of a graduate student clinician, a minimally verbal child with autism spectrum disorder, and the child's parent. Coaching and intervention occurred during an interprofessional summer clinic that included graduate student clinicians from special education and speech and hearing sciences departments. The efficacy of short-term instruction, researcher coaching for student clinicians, and student clinician coaching of parents was evaluated using a multiple baseline across participants' design. The dependent variables were student clinician's and parent's use of elicitation techniques (creating communication temptations, waiting, and prompting) and response techniques (naturally reinforcing children's communication and providing spoken language models). Following coaching, parents and student clinicians from all triads increased their use of elicitation and response techniques, with very large effect sizes across all variables. Visual analysis findings suggest individualized differences and variability across triads. Implications for graduate education and parent coaching programs are discussed.
Topics: Humans; Autism Spectrum Disorder; Mentoring; Male; Communication; Female; Education, Graduate; Child, Preschool; Parents; Child; Speech-Language Pathology
PubMed: 38950566
DOI: 10.1055/s-0044-1787274 -
Annals of Internal Medicine Jul 2024Hernández-Díaz S, Straub L, Bateman BT, et al. N Engl J Med. 2024;390:1069-1079. 38507750.
Hernández-Díaz S, Straub L, Bateman BT, et al. N Engl J Med. 2024;390:1069-1079. 38507750.
PubMed: 38950391
DOI: 10.7326/ANNALS-24-00855-JC -
Developmental Medicine and Child... Jul 2024Schaaf-Yang syndrome (SYS) is a complex neurodevelopmental disorder characterized by autism spectrum disorder, joint contractures, and profound hypothalamic dysfunction.... (Review)
Review
Schaaf-Yang syndrome (SYS) is a complex neurodevelopmental disorder characterized by autism spectrum disorder, joint contractures, and profound hypothalamic dysfunction. SYS is caused by variants in MAGEL2, a gene within the Prader-Willi syndrome (PWS) locus on chromosome 15. In this review, we consolidate decades of research on MAGEL2 to elucidate its physiological functions. Moreover, we synthesize current knowledge on SYS, suggesting that while MAGEL2 loss-of-function seems to underlie several SYS and PWS phenotypes, additional pathomechanisms probably contribute to the distinct and severe phenotype observed in SYS. In addition, we highlight recent therapeutic advances and identify promising avenues for future investigation.
PubMed: 38950199
DOI: 10.1111/dmcn.16018 -
PLoS Neglected Tropical Diseases Jul 2024Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated...
BACKGROUND
Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures.
METHODS
Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used.
RESULTS
A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 μm; HGINV 37 ± 5 μm; WB 28 ± 3 μm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils.
CONCLUSION
The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.
PubMed: 38950061
DOI: 10.1371/journal.pntd.0012302 -
Pediatric Annals Jul 2024Fragile X syndrome is the most commonly inherited form of intellectual disability. Identifying fragile X syndrome at a young age can be quite challenging because the... (Review)
Review
Fragile X syndrome is the most commonly inherited form of intellectual disability. Identifying fragile X syndrome at a young age can be quite challenging because the classical physical features usually present in late childhood or early adolescence; therefore, it is important to consider genetic testing for all males with unexplained developmental delays, intellectual disability, and autism, females with developmental delays, intellectual disability or autism, and a family history of fragile X gene disorders. There is no specific treatment to manage fragile X syndrome. Still, a prompt referral for early intervention is essential to help maximize the child's learning potential, as well as a referral to child psychology if any behavioral concerns are present. It is of paramount importance for families with a history of fragile X syndrome to have access to genetic counseling as it can aid in future reproductive decisions and the risk of future recurrences of this condition. .
Topics: Fragile X Syndrome; Humans; Child; Male; Genetic Testing; Female; Genetic Counseling; Pediatricians; Adolescent; Pediatrics
PubMed: 38949875
DOI: 10.3928/19382359-20240502-08 -
JAMA Network Open Jul 2024Compared with early cord clamping (ECC), umbilical cord milking (UCM) reduces delivery room cardiorespiratory support, hypoxic-ischemic encephalopathy, and therapeutic... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Compared with early cord clamping (ECC), umbilical cord milking (UCM) reduces delivery room cardiorespiratory support, hypoxic-ischemic encephalopathy, and therapeutic hypothermia in nonvigorous near-term and full-term infants. However, UCM postdischarge outcomes are not known.
OBJECTIVE
To determine the 2-year outcomes of children randomized to UCM or ECC at birth in the Milking in Nonvigorous Infants (MINVI) trial.
DESIGN, SETTING, AND PARTICIPANTS
A secondary analysis to evaluate longer-term outcomes of a cluster-randomized crossover trial was conducted from January 9, 2021, to September 25, 2023. The primary trial took place in 10 medical centers in the US, Canada, and Poland from January 5, 2019, to June 1, 2021, and hypothesized that UCM would reduce admission to the neonatal intensive care unit compared with ECC; follow-up concluded September 26, 2023. The population included near-term and full-term infants aged 35 to 42 weeks' gestation at birth who were nonvigorous; families provided consent to complete developmental screening questionnaires through age 2 years.
INTERVENTION
UCM and ECC.
MAIN OUTCOMES AND MEASURES
Ages and Stages Questionnaire, 3rd Edition (ASQ-3) and Modified Checklist for Autism in Toddlers, Revised/Follow-Up (M-CHAT-R/F) questionnaires at ages 22 to 26 months. Intention-to-treat analysis and per-protocol analyses were used.
RESULTS
Among 1730 newborns from the primary trial, long-term outcomes were evaluated in 971 children (81%) who had ASQ-3 scores available at 2 years or died before age 2 years and 927 children (77%) who had M-CHAT-R/F scores or died before age 2 years. Maternal and neonatal characteristics by treatment group were similar, with median birth gestational age of 39 (IQR, 38-40) weeks in both groups; 224 infants (45%) in the UCM group and 201 (43%) in the ECC group were female. The median ASQ-3 total scores were similar (UCM: 255 [IQR, 225-280] vs ECC: 255 [IQR, 230-280]; P = .87), with no significant differences in the ASQ-3 subdomains. Medium- to high-risk M-CHAT-R/F scores were also similar (UCM, 9% [45 of 486] vs ECC, 8% [37 of 441]; P = .86).
CONCLUSIONS AND RELEVANCE
In this secondary analysis of a randomized clinical trial among late near-term and full-term infants who were nonvigorous at birth, ASQ-3 scores at age 2 years were not significantly different between the UCM and ECC groups. Combined with previously reported important short-term benefits, this follow-up study suggests UCM is a feasible, no-cost intervention without longer-term neurodevelopmental risks of cord milking in nonvigorous near-term and term newborns.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03631940.
Topics: Humans; Female; Infant, Newborn; Male; Infant; Umbilical Cord Clamping; Cross-Over Studies; Umbilical Cord; Hypoxia-Ischemia, Brain; Child, Preschool
PubMed: 38949814
DOI: 10.1001/jamanetworkopen.2024.16870 -
Journal of Autism and Developmental... Jun 2024
PubMed: 38949759
DOI: 10.1007/s10803-024-06442-y