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Cells Feb 2020Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid... (Review)
Review
Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degrees of mental retardation, autism, ataxia, and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved curative therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials, and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs, and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between researchers and patients.
Topics: Adult; Amino Acid Metabolism, Inborn Errors; Animals; Child; Clinical Trials as Topic; Developmental Disabilities; Disease Models, Animal; Enzyme Replacement Therapy; Genetic Therapy; Humans; Mice; Molecular Targeted Therapy; Mutation; Succinate-Semialdehyde Dehydrogenase; gamma-Aminobutyric Acid
PubMed: 32093054
DOI: 10.3390/cells9020477 -
International Journal of Palliative... May 2021Of the 40 000 children who die annually in the US, thousands are admitted to hospice care. Little is known about the mental health and developmental disabilities of...
BACKGROUND
Of the 40 000 children who die annually in the US, thousands are admitted to hospice care. Little is known about the mental health and developmental disabilities of these children.
AIMS
To describe the mental health and developmental disabilities of children who are admitted to hospice care and compare this across age groups.
METHODS
The 2011 to 2013 US Medicaid files were used. The sample included 6195 children with a diagnosis of a mental health and/or developmental disability. Comparisons were calculated using the Pearson chi-square test.
RESULTS
Mental health conditions, including anxiety (31.0%), depression (33.1%), behavioural disorders (33.9%) and affective disorders (34.8%), were highest among children aged between 15 and 20 years. Developmental delays were common in children under a year, while intellectual disabilities were highest in the 15 to 20 years age group.
CONCLUSIONS
Nurses have an important role in understanding the mental health and developmental disabilities of children admitted to hospice care.
Topics: Adolescent; Child; Developmental Disabilities; Hospice Care; Hospice and Palliative Care Nursing; Hospitalization; Humans; Mental Health; United States; Young Adult
PubMed: 34038179
DOI: 10.12968/ijpn.2021.27.3.124 -
Developmental Medicine and Child... Jul 2022
Topics: Child; Developmental Disabilities; Humans; Intellectual Disability; Language
PubMed: 35642089
DOI: 10.1111/dmcn.15231 -
Journal of Autism and Developmental... Jun 2021Amidst the ongoing novel Coronavirus disease pandemic, children with developmental disabilities warrant specific attention to minimise having disproportionate... (Review)
Review
Amidst the ongoing novel Coronavirus disease pandemic, children with developmental disabilities warrant specific attention to minimise having disproportionate consequences. These children are especially vulnerable to the effects of the pandemic due to (1) Greater healthcare needs, (2) Dependency on community-based services and (3) Mental health concerns. Healthcare professionals, public health systems and the society needs to come together to advocate for these children by optimising access to healthcare and community intervention services, promoting mental well-being and caregiver welfare. The consequences of missed present-day opportunities might only be evident in the years to come in these children. Hence, despite the prolonged pandemic, with consequent limitations in availability of resources, children with developmental disabilities should continue to be supported.
Topics: Autism Spectrum Disorder; COVID-19; Child; Developmental Disabilities; Health Personnel; Health Services Accessibility; Humans; Mental Health; Pandemics; SARS-CoV-2
PubMed: 32816170
DOI: 10.1007/s10803-020-04670-6 -
Obstetrics and Gynecology Nov 2022To compare the risk of interpersonal violence experienced by pregnant and postpartum individuals with physical disabilities, sensory disabilities, or intellectual or...
OBJECTIVE
To compare the risk of interpersonal violence experienced by pregnant and postpartum individuals with physical disabilities, sensory disabilities, or intellectual or developmental disabilities with those without disabilities, and to examine whether a prepregnancy history of interpersonal violence puts individuals with disabilities, at excess risk of interpersonal violence in the perinatal period.
METHOD
This population-based study included all individuals aged 15-49 years with births in Ontario, Canada, from 2004 to 2019. Individuals with physical (n=147,414), sensory (n=47,459), intellectual or developmental (n=2,557), or multiple disabilities (n=9,598) were compared with 1,594,441 individuals without disabilities. The outcome was any emergency department visit, hospital admission, or death related to physical, sexual, or psychological violence between fertilization and 365 days postpartum. Relative risks (RRs) were adjusted for baseline social and health characteristics. Relative excess risk due to interaction (RERI) was estimated from the joint effects of disability and prepregnancy violence history; RERI>0 indicated positive interaction.
RESULTS
Individuals with physical (0.8%), sensory (0.7%), intellectual or developmental (5.3%), or multiple disabilities (1.8%) were more likely than those without disabilities (0.5%) to experience perinatal interpersonal violence. The adjusted RR was 1.40 (95% CI 1.31-1.50) in those with physical disabilities, 2.39 (95% CI 1.98-2.88) in those with intellectual or developmental disabilities, and 1.96 (95% CI 1.66-2.30) in those with multiple disabilities. Having both a disability and any violence history produced a positive interaction for perinatal interpersonal violence (adjusted RERI 0.87; 95% CI 0.47-1.29).
CONCLUSION
The perinatal period is a time of relative high risk for interpersonal violence among individuals with pre-existing disabilities, especially those with a history of interpersonal violence.
Topics: Humans; Pregnancy; Female; Child; Intellectual Disability; Pregnancy Complications; Disabled Persons; Violence; Ontario; Developmental Disabilities
PubMed: 36201763
DOI: 10.1097/AOG.0000000000004950 -
Developmental Medicine and Child... Jun 2021
Topics: Child; Developing Countries; Developmental Disabilities; Humans; Mainstreaming, Education
PubMed: 33973239
DOI: 10.1111/dmcn.14864 -
Developmental Medicine and Child... Aug 2022The number of diagnoses of developmental disorders is on the rise and the use of labels for developmental disorders, such as attention-deficit/hyperactivity disorder and... (Review)
Review
The number of diagnoses of developmental disorders is on the rise and the use of labels for developmental disorders, such as attention-deficit/hyperactivity disorder and autism spectrum disorder, is widening. Diagnostic labels can play an important role in helping those who display atypical behaviour and their caregivers to cope with associated challenges and, possibly, to get treatment. But these labels are increasingly contested and associated with a variety of harmful effects. In this paper, we analyze the role diagnostic labels can play in four different contexts (scientific, therapeutic, social, and administrative) and identify what various stakeholders stand to gain or lose with continued, expanded, or abolished use of those labels. Our analysis reveals labels serve different purposes in each of these contexts, benefitting different stakeholders. Any overall evaluation, critique, or defence of labels needs to consider the interests of all stakeholders in these contexts.
Topics: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Developmental Disabilities; Humans
PubMed: 35191027
DOI: 10.1111/dmcn.15177 -
Neurochemistry International Dec 2019Air pollution is an important contributor to the global burden of disease, particularly to respiratory and cardiovascular diseases. In recent years, evidence is... (Review)
Review
Air pollution is an important contributor to the global burden of disease, particularly to respiratory and cardiovascular diseases. In recent years, evidence is accumulating that air pollution may adversely affect the nervous system as shown by human epidemiological studies and by animal models. Age appears to play a relevant role in air pollution-induced neurotoxicity, with growing evidence suggesting that air pollution may contribute to neurodevelopmental and neurodegenerative diseases. Traffic-related air pollution (e.g. diesel exhaust) is an important contributor to urban air pollution, and fine and ultrafine particulate matter (PM) may possibly be its more relevant component. Air pollution is associated with increased oxidative stress and inflammation both in the periphery and in the nervous system, and fine and ultrafine PM can directly access the central nervous system. This short review focuses on the adverse effects of air pollution on the developing brain; it discusses some characteristics that make the developing brain more susceptible to toxic effects, and summarizes the animal and human evidence suggesting that exposure to elevated air pollution is associated with a number of behavioral and biochemical adverse effects. It also discusses more in detail the emerging evidence of an association between perinatal exposure to air pollution and increased risk of autism spectrum disorder. Some of the common mechanisms that may underlie the neurotoxicity and developmental neurotoxicity of air pollution are also discussed. Considering the evidence presented in this review, any policy and legislative effort aimed at reducing air pollution would be protective of children's well-being.
Topics: Air Pollutants; Air Pollution; Animals; Autism Spectrum Disorder; Brain; Child; Developmental Disabilities; Female; Humans; Male; Neurotoxicity Syndromes; Pregnancy
PubMed: 31626830
DOI: 10.1016/j.neuint.2019.104580 -
Journal of Neurodevelopmental Disorders May 2022Intellectual and Developmental Disabilities (IDDs), such as Down syndrome, Fragile X syndrome, Rett syndrome, and autism spectrum disorder, usually manifest at birth or... (Review)
Review
Intellectual and Developmental Disabilities (IDDs), such as Down syndrome, Fragile X syndrome, Rett syndrome, and autism spectrum disorder, usually manifest at birth or early childhood. IDDs are characterized by significant impairment in intellectual and adaptive functioning, and both genetic and environmental factors underpin IDD biology. Molecular and genetic stratification of IDDs remain challenging mainly due to overlapping factors and comorbidity. Advances in high throughput sequencing, imaging, and tools to record behavioral data at scale have greatly enhanced our understanding of the molecular, cellular, structural, and environmental basis of some IDDs. Fueled by the "big data" revolution, artificial intelligence (AI) and machine learning (ML) technologies have brought a whole new paradigm shift in computational biology. Evidently, the ML-driven approach to clinical diagnoses has the potential to augment classical methods that use symptoms and external observations, hoping to push the personalized treatment plan forward. Therefore, integrative analyses and applications of ML technology have a direct bearing on discoveries in IDDs. The application of ML to IDDs can potentially improve screening and early diagnosis, advance our understanding of the complexity of comorbidity, and accelerate the identification of biomarkers for clinical research and drug development. For more than five decades, the IDDRC network has supported a nexus of investigators at centers across the USA, all striving to understand the interplay between various factors underlying IDDs. In this review, we introduced fast-increasing multi-modal data types, highlighted example studies that employed ML technologies to illuminate factors and biological mechanisms underlying IDDs, as well as recent advances in ML technologies and their applications to IDDs and other neurological diseases. We discussed various molecular, clinical, and environmental data collection modes, including genetic, imaging, phenotypical, and behavioral data types, along with multiple repositories that store and share such data. Furthermore, we outlined some fundamental concepts of machine learning algorithms and presented our opinion on specific gaps that will need to be filled to accomplish, for example, reliable implementation of ML-based diagnosis technology in IDD clinics. We anticipate that this review will guide researchers to formulate AI and ML-based approaches to investigate IDDs and related conditions.
Topics: Artificial Intelligence; Autism Spectrum Disorder; Child; Child, Preschool; Developmental Disabilities; Humans; Infant, Newborn; Intellectual Disability; Machine Learning
PubMed: 35501679
DOI: 10.1186/s11689-022-09438-w -
Clinics in Perinatology Sep 2020Many observational studies have shown that infants with blood pressures (BPs) that are in the lower range for their gestational age tend to have increased complications... (Review)
Review
Many observational studies have shown that infants with blood pressures (BPs) that are in the lower range for their gestational age tend to have increased complications such as an increased rate of significant intraventricular hemorrhage and adverse long-term outcome. This relationship does not prove causation nor should it create an indication for treatment. However, many continue to intervene with medication for low BP on the assumption that an increase in BP will result in improved outcome. Only adequately powered prospective randomized controlled trials can answer the question of whether individual treatments of low BP are beneficial.
Topics: Blood Pressure; Cardiac Output; Cerebral Intraventricular Hemorrhage; Child Development; Developmental Disabilities; Enterocolitis, Necrotizing; Heart Rate; Hemodynamics; Humans; Hypotension; Infant, Newborn; Infant, Premature; Myocardial Contraction; Oxygen
PubMed: 32713451
DOI: 10.1016/j.clp.2020.05.011