BACKGROUND: Despite reported physical and functional improvements with aerobic and sprint interval training (SIT) protocols in individuals with intellectual disability (ID), it is not known if these interventions\' effectivity would promote improvements in cardiac autonomic modulation. This study aimed to investigate if a 6-month SIT or a continuous aerobic programme could enhance physical performance and cardiac autonomic modulation at rest, during physical activity (PA) and after it in older adults with an ID.
METHODS: This is a randomised control trial. Participants with ID (age: 50.58 ± 7.25) were allocated to one of three groups [multicomponent aerobic training group (MATG), multicomponent interval sprint training group (MISTG) and control group (CG)]. The programmes lasted 24 weeks, with three sessions/week, 75-90 min per session. The HRV was analysed at rest and recovery, the delta of heart rate (HR) was analysed during 6MWT, and the HR t-off kinetics was analysed in recovery after 6MWT.
RESULTS: There were not found differences between groups, moments, or interaction for cardiac autonomic modulation at rest and recovery. During exercise, only MSITG showed a significant increase of HR between rest and the first 30 s of exercise (P < 0.05). Physical performance increased only in MSITG (P < 0.05), while CG showed a significant reduction (P < 0.01).
CONCLUSIONS: The MSITG improved the physical performance and the vagal withdrawal at the beginning of the submaximal exercise. These findings suggest that high-intensity exercise may positively impact baroreflex function, mitigating the decline in autonomic reflex response capacity associated with aging in individuals with ID.

This research analyzes the clinical data, whole-exome sequencing results, and in vitro minigene functional experiments of a child with developmental delay and intellectual disability. The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth and has shown developmental delay. Rehabilitation training was administered between the ages of one and two. There were no other significant family medical histories. Through comprehensive family exome genetic testing, a hemizygous variant in the 11th exon of the OPHN1 gene was identified in the affected child: c.1025 + 1G > A. Family segregation analysis confirmed the presence of this variant in the patient\'s mother, which had not been previously reported. According to the ACMG guidelines, this variant was classified as a likely pathogenic variant. In response to this variant, an in vitro minigene functional experiment was designed and conducted, confirming that the mutation affects the normal splicing of the gene\'s mRNA, resulting in a 56 bp retention on the left side of Intron 11. It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.

BACKGROUND: Intellectual disability (ID) is a neurodevelopmental condition affecting around 2% of children and young adults worldwide, characterized by deficits in intellectual functioning and adaptive behavior. Genetic factors contribute to the development of ID phenotypes, including mutations and structural changes in chromosomes. Pathogenic variants in the HCFC1 gene cause X-linked mental retardation syndrome, also known as Siderius type X-linked mental retardation. The MN1 gene is necessary for palate development, and mutations in this gene result in a genetic condition called CEBALID syndrome.
METHODS: Exome sequencing was used to identify the disease-causing variants in two affected families, A and B, from various regions of Pakistan. Affected individuals in these two families presented ID, developmental delay, and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing.
RESULTS: In an X-linked family A, a novel hemizygous missense variant (c.5705G > A; p.Ser1902Asn) in the HCFC1 gene (NM_005334.3) was identified, while in family B exome sequencing revealed a heterozygous nonsense variant (c.3680 G > A; p. Trp1227Ter) in exon-1 of the MN1 gene (NM_032581.4). Sanger sequencing confirmed the segregation of these variants with ID in each family.
CONCLUSIONS: The investigation of two Pakistani families revealed pathogenic genetic variants in the HCFC1 and MN1 genes, which cause ID and expand the mutational spectrum of these genes.

BACKGROUND:  Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with a wide clinical, cognitive, and behavioral expressivity.
OBJECTIVE:  To assess the neuropsychological profile of individuals clinically diagnosed with TSC and the factors that could significantly impact their cognitive development.
METHODS:  A total of 62 individuals with ages ranging from 3 to 38 years were followed up in a tertiary attention hospital in Southern Brazil, and they were assessed using a standard battery and the Vineland Adaptive Behavior Scales, when intellectual disability was observed.
RESULTS:  History of epilepsy was found in 56 participants (90.3%), and 31 (50%) presented an intellectual disability. Among the other half of TSC individuals without intellectual disability, 8 (12.9%) presented borderline classification, 20 (32.2%) presented average scores, and 3 (4.8%) were above average. In total, 17 participants (27.4%) fulfilled the diagnostic criteria for autism spectrum disorder. The results of the multiple linear regression analysis suggested that seizures, age at diagnosis, visual perception, and general attention significantly impact cognitive performance indexes.
CONCLUSIONS:  The present study suggests that the occurrence of epileptic seizures and older age at diagnosis contribute to higher impairment in the domains of cognitive development, underlining the importance of early diagnosis and the prevention of epileptic seizures or their rapid control. The development of attentional skills, visual perception, and executive functions must be followed up.
BACKGROUND:  O complexo da esclerose tuberosa (CET) é uma doença genética autossômica dominante com ampla expressividade clínica, cognitiva e comportamental.
OBJECTIVE:  Avaliar o perfil neuropsicológico de indivíduos com diagnóstico clínico de CET e os fatores que poderiam impactar significativamente o seu desenvolvimento cognitivo. MéTODOS:  Ao todo, 62 indivíduos com idades entre 3 e 38 anos foram acompanhados em um hospital terciário do Sul do Brasil e avaliados por meio de uma bateria padrão e das Escalas de Comportamento Adaptativo Vineland, quando observada deficiência intelectual.
RESULTS:  Encontrou-se histórico de epilepsia em 56 participantes (90,3%) e de deficiência intelectual em 31 (50%). Quanto à outra metade dos indivíduos com CET sem deficiência intelectual, 8 (12,9%) apresentaram classificação limítrofe, 20 (32,2%) apresentaram pontuações médias e 3 (4,8%) estavam acima da média. No total, 17 participantes (27,4%) preenchiam os critérios diagnósticos para o transtorno do espectro autista. Os resultados da análise de regressão linear múltipla sugeriram que as crises epilépticas, a idade ao diagnóstico, a percepção visual e a atenção geral impactam significativamente os índices de desempenho cognitivo. CONCLUSãO:  Este estudo sugere que a ocorrência de crises epilépticas e a maior idade ao diagnóstico contribuem para um maior comprometimento nos domínios do desenvolvimento cognitivo, e destaca-se a importância do diagnóstico precoce e da prevenção das crises epilépticas ou do seu rápido controle. O desenvolvimento de habilidades de atenção, percepção visual e funções executivas deve ser acompanhado.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a diverse profile of cognitive functions. Heterogeneity is observed among both baseline and comorbid features concerning the diversity of neuropathology in autism. Symptoms vary depending on the developmental stage, level of severity, or comorbidity with other medical or psychiatric diagnoses such as intellectual disability, epilepsy, and anxiety disorders.
METHODS: The neurodiversity movement does not face variations in neurological and cognitive development in ASD as deficits but as normal non-pathological human variations. Thus, ASD is not identified as a neurocognitive pathological disorder that deviates from the typical, but as a neuro-individuality, a normal manifestation of a neurobiological variation within the population.
RESULTS: In this light, neurodiversity is described as equivalent to any other human variation, such as ethnicity, gender, or sexual orientation. This review will provide insights about the neurodiversity approach in children and adults with ASD. Using a neurodiversity approach can be helpful when working with children who have autism spectrum disorder (ASD).
CONCLUSIONS: This method acknowledges and values the various ways that people with ASD interact with one another and experience the world in order to embrace the neurodiversity approach when working with children with ASD.

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.

Neurodevelopmental disorders (NDDs) include a broad spectrum of pathological conditions that affect >4% of children worldwide, share common features and present a variegated genetic origin. They include clinically defined diseases, such as autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), motor disorders such as Tics and Tourette\'s syndromes, but also much more heterogeneous conditions like intellectual disability (ID) and epilepsy. Schizophrenia (SCZ) has also recently been proposed to belong to NDDs. Relatively common causes of NDDs are copy number variations (CNVs), characterised by the gain or the loss of a portion of a chromosome. In this review, we focus on deletions and duplications at the 16p11.2 chromosomal region, associated with NDDs, ID, ASD but also epilepsy and SCZ. Some of the core phenotypes presented by human carriers could be recapitulated in animal and cellular models, which also highlighted prominent neurophysiological and signalling alterations underpinning 16p11.2 CNVs-associated phenotypes. In this review, we also provide an overview of the genes within the 16p11.2 locus, including those with partially known or unknown function as well as non-coding RNAs. A particularly interesting interplay was observed between MVP and MAPK3 in modulating some of the pathological phenotypes associated with the 16p11.2 deletion. Elucidating their role in intracellular signalling and their functional links will be a key step to devise novel therapeutic strategies for 16p11.2 CNVs-related syndromes.

This article surveys the experiences of historical actors labelled \'mentally defective\' and \'mentally handicapped\' in Britain in the first half of the twentieth century. It decentres institutions and experiences of segregation, and instead foregrounds employment as a way to historicise and make visible the experiences of individuals with intellectual impairments who lived in communities. The article discusses significant opportunities for paid employment, both formal and informal, for disabled people. Periods of economic growth or recession rendered such workers visible, as did efforts to regulate labour markets and wages. The article argues that rather than \'mental age\' becoming dominant in framing intellectual disability, vernacular and negotiable categories of \'wage age\' predominated in workplaces to the mid-twentieth century. Intellectually disabled people adopted precarious strategies of \'getting by\' and while they commonly experienced low wages, could also sustain degrees of community inclusion at the margins of the economy.

UNASSIGNED: Forensic psychiatric patients receive treatment to address their violent and aggressive behavior with the aim of facilitating their safe reintegration into society. On average, these treatments are effective, but the magnitude of effect sizes tends to be small, even when considering more recent advancements in digital mental health innovations. Recent research indicates that wearable technology has positive effects on the physical and mental health of the general population, and may thus also be of use in forensic psychiatry, both for patients and staff members. Several applications and use cases of wearable technology hold promise, particularly for patients with mild intellectual disability or borderline intellectual functioning, as these devices are thought to be user-friendly and provide continuous daily feedback.
UNASSIGNED: In the current randomized crossover trial, we addressed several limitations from previous research and compared the (continuous) usability and acceptance of four selected wearable devices. Each device was worn for one week by staff members and patients, amounting to a total of four weeks. Two of the devices were general purpose fitness trackers, while the other two devices used custom made applications designed for bio-cueing and for providing insights into physiological reactivity to daily stressors and events.
UNASSIGNED: Our findings indicated significant differences in usability, acceptance and continuous use between devices. The highest usability scores were obtained for the two fitness trackers (Fitbit and Garmin) compared to the two devices employing custom made applications (Sense-IT and E4 dashboard). The results showed similar outcomes for patients and staff members.
UNASSIGNED: None of the devices obtained usability scores that would justify recommendation for future use considering international standards; a finding that raises concerns about the adaptation and uptake of wearable technology in the context of forensic psychiatry. We suggest that improvements in gamification and motivational aspects of wearable technology might be helpful to tackle several challenges related to wearable technology.

BACKGROUND: Implementation issues often hinder reaching the potential of care technology to improve daily lives of people with intellectual disabilities. We investigated barriers to and facilitators of implementing different technology modalities (app/social robot/sensor/domotics) in long-term care.
METHODS: Care professionals (N = 83) from 12 Dutch disability care organisations completed a customised measurement instrument for determinants of innovations (MIDI) questionnaire.
RESULTS: Out of 27 determinants, 20 were identified as facilitators and 16 as barriers. We highlight common barriers: few colleagues who work with the technology; no (awareness of) formal ratification of technology use; no arrangements regarding turnover of staff using the technology; unsettling organisational changes; technological defects and limited IT preconditions.
CONCLUSIONS: The results, which could be combined and compared across study sites, provide insight into which implementation determinants were already well addressed, and where there is ground to gain when implementing care technology in disability care organisations.