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International Review of Cell and... 2015Physiological development requires precise spatiotemporal regulation of cellular and molecular processes. Disruption of these key events can generate developmental... (Review)
Review
Physiological development requires precise spatiotemporal regulation of cellular and molecular processes. Disruption of these key events can generate developmental toxicity in the form of teratogenesis or mortality. The mechanism behind many developmental toxicants remains unknown. While recent work has focused on the unfolded protein response (UPR), oxidative stress, and apoptosis in the pathogenesis of disease, few studies have addressed their relationship in developmental toxicity. Redox regulation, UPR, and apoptosis are essential for physiological development and can be disturbed by a variety of endogenous and exogenous toxicants to generate lethality and diverse malformations. This review examines the current knowledge of the role of oxidative stress, UPR, and apoptosis in physiological development as well as in developmental toxicity, focusing on studies and advances in vertebrates model systems.
Topics: Animals; Apoptosis; Developmental Disabilities; Humans; Oxidative Stress; Teratogenesis; Unfolded Protein Response
PubMed: 26008783
DOI: 10.1016/bs.ircmb.2015.02.002 -
Current Opinion in Neurology Apr 2016Despite significant progress in recognizing the biological bases of autism spectrum disorder, diagnosis and treatment rely primarily on subjective evaluation of... (Review)
Review
PURPOSE OF REVIEW
Despite significant progress in recognizing the biological bases of autism spectrum disorder, diagnosis and treatment rely primarily on subjective evaluation of behavior. This review highlights the challenges unique to neurodevelopmental disorders that have limited biomarker development.
RECENT FINDINGS
The field of neurodevelopmental disorders requires objective quantification of biological processes to enable designation of subgroups likely to benefit from specific treatments, index diagnostic status/risk, demonstrate engagement of targeted systems, and provide more rapid assessment of change than traditional clinical observation and caregiver report measures.
SUMMARY
Useful biomarkers for neurodevelopmental disorders must be reliable across development, evident at the individual level, and specific to a unit of analysis, be it diagnostic status or functional process. The ultimate value of biomarkers for neurodevelopmental disorders will relate to their ease of use, cost, scalability, sensitivity, and methodological objectivity.
Topics: Age Factors; Autism Spectrum Disorder; Biomarkers; Developmental Disabilities; Humans; Individuality; Neurodevelopmental Disorders
PubMed: 26844621
DOI: 10.1097/WCO.0000000000000300 -
Paediatrics and International Child... Nov 2014There is increasing international interest in the links between malnutrition and disability: both are major global public health problems, both are key human rights... (Review)
Review
There is increasing international interest in the links between malnutrition and disability: both are major global public health problems, both are key human rights concerns, and both are currently prominent within the global health agenda. In this review, interactions between the two fields are explored and it is argued that strengthening links would lead to important mutual benefits and synergies. At numerous points throughout the life-cycle, malnutrition can cause or contribute to an individual's physical, sensory, intellectual or mental health disability. By working more closely together, these problems can be transformed into opportunities: nutrition services and programmes for children and adults can act as entry points to address and, in some cases, avoid or mitigate disability; disability programmes can improve nutrition for the children and adults they serve. For this to happen, however, political commitment and resources are needed, as are better data.
Topics: Adult; Child, Preschool; Developmental Disabilities; Female; Global Health; Health Policy; Health Services Administration; Humans; Infant; Infant, Newborn; Malnutrition; Pregnancy
PubMed: 25309998
DOI: 10.1179/2046905514Y.0000000156 -
CNS Neuroscience & Therapeutics Nov 2016
Topics: Developmental Disabilities; Diagnostic Errors; Humans; Sleep
PubMed: 27779373
DOI: 10.1111/cns.12657 -
Experimental & Molecular Medicine Mar 2021Zebrafish have several advantages compared to other vertebrate models used in modeling human diseases, particularly for large-scale genetic mutant and therapeutic... (Review)
Review
Zebrafish have several advantages compared to other vertebrate models used in modeling human diseases, particularly for large-scale genetic mutant and therapeutic compound screenings, and other biomedical research applications. With the impactful developments of CRISPR and next-generation sequencing technology, disease modeling in zebrafish is accelerating the understanding of the molecular mechanisms of human genetic diseases. These efforts are fundamental for the future of precision medicine because they provide new diagnostic and therapeutic solutions. This review focuses on zebrafish disease models for biomedical research, mainly in developmental disorders, mental disorders, and metabolic diseases.
Topics: Animals; Biomedical Research; Developmental Disabilities; Disease Models, Animal; Humans; Mental Disorders; Metabolic Diseases; Zebrafish
PubMed: 33649498
DOI: 10.1038/s12276-021-00571-5 -
Genetics in Medicine : Official Journal... Mar 2021Genetic testing is routine practice for individuals with unexplained developmental disabilities and multiple congenital anomalies. However, current testing pathways can...
PURPOSE
Genetic testing is routine practice for individuals with unexplained developmental disabilities and multiple congenital anomalies. However, current testing pathways can be costly and time consuming, and the diagnostic yield low. Genome-wide sequencing, including exome sequencing (ES) and genome sequencing (GS), can improve diagnosis, but at a higher cost. This study aimed to assess the cost-effectiveness of genome-wide sequencing in Ontario, Canada.
METHODS
A cost-effectiveness analysis was conducted using a discrete event simulation from a public payer perspective. Six strategies involving ES or GS were compared. Outcomes reported were direct medical costs, number of molecular diagnoses, number of positive findings, and number of active treatment changes.
RESULTS
If ES was used as a second-tier test (after the current first-tier, chromosomal microarray, fails to provide a diagnosis), it would be less costly and more effective than standard testing (CAN$6357 [95% CI: 6179-6520] vs. CAN$8783 per patient [95% CI: 2309-31,123]). If ES was used after standard testing, it would cost an additional CAN$15,228 to identify the genetic diagnosis for one additional patient compared with standard testing. The results remained robust when parameters and assumptions were varied.
CONCLUSION
ES would likely be cost-saving if used earlier in the diagnostic pathway.
Topics: Abnormalities, Multiple; Child; Cost-Benefit Analysis; Developmental Disabilities; Humans; Ontario; Exome Sequencing
PubMed: 33110268
DOI: 10.1038/s41436-020-01012-w -
American Journal of Medical Genetics.... Sep 2015Disorders resulting from 5p deletions (5p-) were first recognized by Lejeune et al. in 1963 [Lejeune et al. (1963); C R Hebd Seances Acad Sci 257:3098-3102]. 5p- is... (Review)
Review
Disorders resulting from 5p deletions (5p-) were first recognized by Lejeune et al. in 1963 [Lejeune et al. (1963); C R Hebd Seances Acad Sci 257:3098-3102]. 5p- is caused by partial or total deletion of the short arm of chromosome 5. The most recognizable phenotype is characterized by a high-pitched cry, dysmorphic features, poor growth, and developmental delay. This report reviews 5p- disorders and their molecular basis. Hemizygosity for genes located within this region have been implicated in contributing to the phenotype. A review of the genes on 5p which may be dosage sensitive is summarized. Because of the growing knowledge of these specific genes, future directions to explore potential targeted therapies for individuals with 5p- are discussed. © 2015 Wiley Periodicals, Inc.
Topics: Chromosome Deletion; Chromosomes, Human, Pair 5; Developmental Disabilities; Humans; Phenotype
PubMed: 26235846
DOI: 10.1002/ajmg.c.31444 -
The Clinical Neuropsychologist Feb 2017Early detection of children with developmental delay is crucial for determining which children require close surveillance and intervention services. For many decades,... (Review)
Review
OBJECTIVE
Early detection of children with developmental delay is crucial for determining which children require close surveillance and intervention services. For many decades, the Bayley Scales has been the most widely used objective measure of early developmental delay, both in clinical and research settings. Significant structural changes were incorporated in the most recent edition, the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). This article reviews the psychometric properties of the Bayley-III and investigates criticisms raised on the Bayley-III, namely that it overestimates developmental status and is a poor predictor of later functioning.
METHOD
This critical review examines the literature on the Bayley-III, which was released in 2006.
RESULTS
The Cognitive, Language, and Motor composites of the Bayley-III overestimate development, resulting in an under-identification of children with developmental delay. A range of strategies have been proposed for dealing with the inflated scores on the Bayley-III, none of which are ideal. Evidence to date suggests that the Bayley-III is a poor predictor of later cognitive and motor impairments.
CONCLUSIONS
The Bayley-III needs new norms, or alternatively, it may be time for a new edition of the Bayley Scales.
Topics: Child; Child Development; Child, Preschool; Cognition; Developmental Disabilities; Female; Humans; Infant; Language Development; Male; Motor Skills; Neuropsychological Tests; Predictive Value of Tests; Psychometrics
PubMed: 27687612
DOI: 10.1080/13854046.2016.1216518 -
Pediatric Neurology Feb 2015Advances in obstetric and neonatal medical care and assisted reproductive technology have increased the rates of preterm birth, decreased preterm mortality rates, and... (Review)
Review
BACKGROUND
Advances in obstetric and neonatal medical care and assisted reproductive technology have increased the rates of preterm birth, decreased preterm mortality rates, and lowered the limit of viability. However, morbidity in survivors, including neurodevelopmental disabilities, has increased, especially in extremely preterm infants born at ≤25 weeks' gestation. A better understanding of the prevalence and patterns of adverse neurodevelopmental outcomes in extremely preterm infants is important for patient care, counseling of families, and research.
METHODS
The PubMed and Ovid Medline databases were searched for full text articles published between 1999 and 2013 in English that reported neurodevelopmental outcomes after extreme prematurity, and a review of identified relevant cohort studies was performed.
RESULTS
Extreme prematurity of 22 to 25 weeks' gestation is associated with an overall high mortality of ≥50%. High rates (17% to 59%) of severe neurodevelopmental disabilities occur among survivors on short-term follow-up. The rates of surviving unimpaired or minimally impaired are 6% to 20% for live-born infants at ≤25 weeks' gestation and <5% for infants born at 22 and 23 weeks' gestation. Long-term adverse outcomes after extreme prematurity include intellectual disability (5% to 36%), cerebral palsy (9% to 18%), blindness (0.7% to 9%), and deafness (2% to 4%). Milder degrees of disability involving cognition, behavior, and learning are increasingly recognized among older preterm children, teens, and young adults.
CONCLUSIONS
Infants who are born at ≤25 weeks' gestation, especially those born at 22 and 23 weeks' gestation, have a very low likelihood of surviving little or no impairment. Nearly half of surviving extremely premature infants have significant neurodevelopmental disabilities on short- and long-term follow-up. Instituting early intervention programs, providing family support, and establishing special educational school programs can pay high dividends and lead to brighter futures and, hence, help improve neurodevelopmental outcome of preterm infants.
Topics: Developmental Disabilities; Gestational Age; Humans; Infant, Extremely Premature; Infant, Premature, Diseases; Nervous System Diseases; PubMed
PubMed: 25497122
DOI: 10.1016/j.pediatrneurol.2014.10.027 -
Journal of Intellectual Disability... Aug 2022The COVID-19 pandemic has significantly impacted family caregivers of adults with intellectual and developmental disabilities (IDD). This study evaluated a virtual...
BACKGROUND
The COVID-19 pandemic has significantly impacted family caregivers of adults with intellectual and developmental disabilities (IDD). This study evaluated a virtual course for family caregivers from across Canada, focused on supporting the mental health and well-being of adults with IDD and their families. The evaluation examined the feasibility and acceptability of the course, as well as the impact of the intervention on participants' overall health and well-being.
METHODS
The 6-week virtual course, informed by a parallel Extension for Community Healthcare Outcomes (ECHO) course for service providers, combined didactic instruction with applied activities. A total of 126 family caregiver course participants consented to be part of the research evaluation delivered over three cycles between October 2020 and April 2021. Attendance was measured at each weekly session. Satisfaction was assessed weekly and post-program. Learning, self-efficacy, and well-being were assessed pre- and post-course, and again at follow-up (8 weeks post-course). Mixed-effects models assessed changes between and within individuals across time.
RESULTS
Participants had consistent attendance, low-dropout rates, and reported high satisfaction, with 93% of participants reporting that their expectations for the course were met. Compared with pre-course, participants reported improved self-efficacy and well-being post-course, which were maintained at follow-up.
CONCLUSIONS
An interactive and applied virtual education course delivered to a large group of family caregivers of adults with IDD was both feasible and acceptable. It positively impacted participants' well-being by offering much needed mental health support and creating a peer-led community of practice.
Topics: Adult; COVID-19; Caregivers; Child; Developmental Disabilities; Humans; Mental Health; Pandemics
PubMed: 35915874
DOI: 10.1111/jir.12965