Caring for Children with an Autism Spectrum Disorder:Factors Associating with Health- and Care-Related Quality of Life of the Caregivers

This study investigated the association of child, caregiver, and caregiving measurements with the quality of life (QoL) in 81 caregivers (mostly parents) of clinically referred children with autism spectrum disorder (ASD). We used the EuroQol five-dimensional (EQ-5D) questionnaire and the care-related QoL questionnaire (CarerQol) to respectively assess health-related QoL and care-related QoL. Health-related QoL was associated with the caregiver's internalizing problems and adaptive coping, explaining 38% of the variance. Parenting stress and adaptive coping were associated with the care-related QoL and explained 60% of the variance. Child variables were not associated with the caregiver's health- and care-related QoL if caregiver and caregiving variables were taken into account. Findings indicate the importance of the caregiver's mental health, coping, and parenting stress in caring for children with ASD

Diversity and pathogenicity of the Ceratocystidaceae associated with cacao agroforests in Cameroon

Knowledge of the diversity and ecology of plant pathogenic fungi in cacao agroforests and surrounding natural ecosystems can inform the development of sustainable management strategies for new cacao disease outbreaks. In this study, we investigated the occurrence of fungi related to the Ceratocystisdaceae and their nitidulid beetle vectors in cacao agroforests in Cameroon, under diverse agroecological conditions. The fungi and their vectors were collected from artificially induced stem wounds on cacao and associated shade trees. Collections were also made from abandoned cacao pod husks and other tree wounds within and around plantations. Fungal isolates were identified using DNA sequence-based phylogenies and morphological comparisons, and two representatives of each species were evaluated for pathogenicity on cacao. Five species of Ceratocystidaceae were recovered, including Huntiella chlamydoformis sp. nov., H. pycnanthi sp. nov. and H. moniliformis, as well as Thielaviopsis cerberus and Th. ethacetica. The incidence of these fungi appeared to be influenced by the prevailing agroecological conditions. Nitidulid beetles in the genus Brachypeplus were found to be their most common insect associates on cacao. Both Th. ethacetica and H. pycnanthi produced extensive lesions after inoculation on branches of mature cacao trees, while Th. ethacetica also caused pod rot. Although their impact remains unknown, fungi in the Ceratocystidaceae and their nitidulid beetle vectors are common and likely contribute to the parasitic pressure in Cameroonian cacao agrosystems.NRF-DST Centre of Excellence in Tree Health Biotechnology (CTHB) of South Africa and the Department of Corporate International Relations of the University of Pretoria through a postgraduate ‘study abroad grant’.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-30592017-01-31hb2016Forestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog

Cannabidiol (Epidyolex®) for severe behavioral manifestations in patients with tuberous sclerosis complex, mucopolysaccharidosis type III and fragile X syndrome:protocol for a series of randomized, placebo-controlled N-of-1 trials

Background: Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design. Methods: We aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N-of-1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants’ natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N-of-1 trials. Discussion: These N-of-1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level. Trial registration: EudraCT: 2021-003250-23, registered 25 August 2022, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL .</p

Cannabidiol (Epidyolex®) for severe behavioral manifestations in patients with tuberous sclerosis complex, mucopolysaccharidosis type III and fragile X syndrome:protocol for a series of randomized, placebo-controlled N-of-1 trials

Background: Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design. Methods: We aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N-of-1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants’ natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N-of-1 trials. Discussion: These N-of-1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level. Trial registration: EudraCT: 2021-003250-23, registered 25 August 2022, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL .</p

Temporal regularity of the environment drives time perception

It’s reasonable to assume that a regularly paced sequence should be perceived as regular, but here we show that perceived regularity depends on the context in which the sequence is embedded. We presented one group of participants with perceptually regularly paced sequences, and another group of participants with mostly irregularly paced sequences (75% irregular, 25% regular). The timing of the final stimulus in each sequence could be varied. In one experiment, we asked whether the last stimulus was regular or not. We found that participants exposed to an irregular environment frequently reported perfectly regularly paced stimuli to be irregular. In a second experiment, we asked participants to judge whether the final stimulus was presented before or after a flash. In this way, we were able to determine distortions in temporal perception as changes in the timing necessary for the sound and the flash to be perceived synchronous. We found that within a regular context, the perceived timing of deviant last stimuli changed so that the relative anisochrony appeared to be perceptually decreased. In the irregular context, the perceived timing of irregular stimuli following a regular sequence was not affected. These observations suggest that humans use temporal expectations to evaluate the regularity of sequences and that expectations are combined with sensory stimuli to adapt perceived timing to follow the statistics of the environment. Expectations can be seen as a-priori probabilities on which perceived timing of stimuli depend

Clinical aspects of a large group of adults with Angelman syndrome

Descriptions of the clinical features of Angelman syndrome (AS) have mainly been focused on children. Here, we describe

Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect

The creatine transporter (CRTR) defect is a recently discovered cause of X-linked intellectual disability for which treatment options have been explored. Creatine monotherapy has not proved effective, and the effect of treatment with L-arginine is still controversial. Nine boys between 8 months and 10 years old with molecularly confirmed CRTR defect were followed with repeated 1H-MRS and neuropsychological assessments during 4–6 years of combination treatment with creatine monohydrate, L-arginine, and glycine. Treatment did not lead to a significant increase in cerebral creatine content as observed with H1-MRS. After an initial improvement in locomotor and personal-social IQ subscales, no lasting clinical improvement was recorded. Additionally, we noticed an age-related decline in IQ subscales in boys affected with the CRTR defect