It has been estimated that autism spectrum disorder (ASD) now affects 1 in 59 children in the United States. Although the cause(s) of ASD remain largely unknown, it is becoming increasingly apparent ...that ASD can no longer be defined simply as a behavioral disorder, but is in effect a rather complex and highly heterogeneous biological disorder. Up until recently the brain was thought to be "immune privileged." However, it is now known that the immune system plays critical roles in the development and functioning of the brain throughout life. Recent evidence from multiple investigators has illustrated the deleterious role that dysregulation of the maternal immune system during gestation can play in the manifestation of changes in neurodevelopment, resulting in the development of neurobehavioral disorders such as ASD. One potential etiologic pathway through which the maternal immune system can interfere with neurodevelopment is through maternal autoantibodies that recognize proteins in the developing fetal brain. This mechanism of pathogenesis is now thought to lead to a subphenotype of ASD that has been termed maternal autoantibody related (MAR) ASD. This review provides an overview of the current research implicating the presence of brain-reactive maternal autoantibodies as a risk factor for MAR ASD.
Risk Assessment and Prevention of Falls Jones, Karen L.; Wu, Tongzhi; Horowitz, Michael
JAMA : the journal of the American Medical Association,
07/2024
Journal Article
The true prevalence, however, remains uncertain because of a lack of population-based studies and inconsistent criteria to define gastroparesis, including variations in the technique used to quantify ...gastric emptying (where scintigraphy remains the gold standard method and stable isotope breath tests and ultrasonography represent acceptable alternatives), the desirable blood glucose levels during the emptying measurement, the magnitude of the delay in gastric emptying regarded as abnormal, and whether the presence of gastrointestinal symptoms represents a prerequisite for the diagnosis. ...in an individual type 2 diabetic patient, the impact of a GLP-1 agonist on postprandial glycemia is likely to be dependent on both the baseline rate of emptying and the choice of GLP-1 agonist.
The rate of gastric emptying is a critical determinant of postprandial glycaemia and, accordingly, is fundamental to maintaining blood glucose homeostasis. Disordered gastric emptying occurs ...frequently in patients with longstanding type 1 diabetes mellitus and type 2 diabetes mellitus (T2DM). A complex bidirectional relationship exists between gastric emptying and glycaemia--gastric emptying accounts for ∼35% of the variance in peak postprandial blood glucose concentrations in healthy individuals and in patients with diabetes mellitus, and the rate of emptying is itself modulated by acute changes in glycaemia. Clinical implementation of incretin-based therapies for the management of T2DM, which diminish postprandial glycaemia, in part by slowing gastric emptying, is widespread. Other therapies for patients with T2DM, which specifically target gastric emptying include pramlintide and dietary-based treatment approaches. A weak association exists between upper gastrointestinal symptoms and the rate of gastric emptying. In patients with severe diabetic gastroparesis, pathological changes are highly variable and are characterized by loss of interstitial cells of Cajal and an immune infiltrate. Management options for patients with symptomatic gastroparesis remain limited in their efficacy, which probably reflects the heterogeneous nature of the underlying pathophysiology.
Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of ...cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA’s Life’s Simple 74 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index <25 kg/m) and 3 ideal health factors (untreated blood pressure <120/<80 mm Hg, untreated total cholesterol <200 mg/dL, and fasting blood glucose <100 mg/dL). In addition, in relation to maintenance of cognitive health, we recommend following previously published guidance from the AHA/American Stroke Association, Institute of Medicine, and Alzheimer’s Association that incorporates control of cardiovascular risks and suggest social engagement and other related strategies. We define optimal brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA’s Life’s Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA’s Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health promotion and disease prevention.
Relatively little research has focused on children and young people (CYP) whose mental health and wellbeing improved during Covid-19 lockdown measures. We aimed to (1) determine the proportion of CYP ...who self-reported improvement in their mental wellbeing during the first Covid-19 lockdown and (2) describe the characteristics of this group in relation to their peers. We conducted a descriptive analysis of data from the 2020 OxWell Student Survey, a self-report, cross-sectional survey of English CYP. A total of 16,940 CYP primarily aged 8–18 years reported on change in mental wellbeing during lockdown. We characterised these CYP in terms of school, home, relational, and lifestyle factors as well as feelings about returning to school. One-third (33%) of CYP reported improved mental wellbeing during the first UK national lockdown. Compared with peers who reported no change or deterioration, a higher proportion of CYP with improved mental wellbeing reported improved relationships with friends and family, less loneliness and exclusion, reduced bullying, better management of school tasks, and more sleep and exercise during lockdown. In conclusion, a sizeable minority of CYP reported improved mental wellbeing during lockdown. Determining the reasons
why
these CYP felt they fared better during lockdown and considering
how
these beneficial experiences can be maintained beyond the pandemic might provide insights into how to promote the future mental health and wellbeing of school-aged CYP. All those working with CYP now have an opportunity to consider whether a systemic shift is needed in order to understand and realise any learnings from experiences during the pandemic.
Abstract Objective To systematically review the correlates of physical activity and sedentary behavior among children in Early Childhood Education and Care (ECEC) services. Appropriate levels of ...physical activity and sedentary behavior are important to promote in ECEC services. Methods A systematic search of 8 databases identified 27 studies published between 1992 and 2015 that met the inclusion criteria. The data were collected and analyzed in 2014 and 2015, and variables were categorized using a Social Ecological Framework. Results Sixty-six variables were identified. The domains of child characteristics (18 studies) and physical environmental factors (17 studies) were most consistently studied, and, for physical activity had the most positive associations. The strongest associations of physical activity were: child's sex and age, children's gross motor coordination, provision of active opportunities for physical activity, and features of outdoor environments (size, use of and presence). The only strong association for sedentary behavior was the presence of outdoor environments. Conclusion The correlates of physical activity and sedentary behavior in ECEC services vary. It appears that the most significant influence from within these settings is the physical environments for both physical activity and sedentary behavior. There was an absence of consistent evidence at the educator and organizational levels. Further research in this area should focus on effective use of space, intentional teaching opportunities and well as professional development for educators with an emphasis on their role as a facilitator of quality experiences. This review has been registered with Prospero, #CRD42014013660.
The identification of an early biomarker for autism spectrum disorder (ASD) would improve the determination of risk, leading to earlier diagnosis and, potentially, earlier intervention and improved ...outcomes.
Data were generated from the Early Markers for Autism study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (n = 370), children with developmental delay (n = 140), and general population (GP) controls (n = 378) were analyzed for 42 different immune markers using a Luminex multiplex platform. Comparisons of immune marker concentrations between groups were examined using logistic regression and partial least squares discriminant analysis.
Children with ASD had significantly increased neonatal levels of interleukin-6 (IL-6) and IL-8 compared with GP controls. An increase in IL-8 was especially significant in the ASD group with early onset compared with the GP group, with an adjusted odds ratio of 1.97 (95% confidence interval, 1.39–2.83; p = .00014). In addition, children with ASD had significantly elevated levels of eotaxin-1, interferon-γ, and IL-12p70 relative to children with developmental delay. We observed no significant differences in levels of immune markers between the developmental delay and GP groups.
Elevated levels of some inflammatory markers in newborn bloodspots indicated a higher degree of immune activation at birth in children who were subsequently diagnosed with ASD. The data from this exploratory study suggest that with further expansion, the development of neonatal bloodspot testing for cytokine/chemokine levels might lead to the identification of biomarkers that provide an accurate assessment of ASD risk at birth.
Gastric emptying is a major determinant of postprandial blood glucose, accounting for ~35% of variance in peak glucose in both healthy individuals and those with type 2 diabetes. Gastric emptying is ...frequently disordered in individuals with diabetes (both abnormally delayed and accelerated). Delayed gastric emptying, i.e. diabetic gastroparesis, may be linked to upper gastrointestinal symptoms for which current treatment remains suboptimal; pharmacological acceleration of delayed emptying is only weakly associated with symptom improvement. Accordingly, the relationship between symptoms and delayed gastric emptying is not simply ‘cause and effect’. In insulin-treated patients, disordered gastric emptying, even when not associated with gastrointestinal symptoms, can cause a mismatch between the onset of insulin action and the availability of absorbed carbohydrate, leading to suboptimal glycaemic control. In patients with type 2 diabetes, interventions that slow gastric emptying, e.g. glucagon-like peptide-1 receptor agonists, reduce postprandial blood glucose. This review focuses on recent insights into the impact of gastric emptying on postprandial blood glucose, effects of diabetes therapy on gastric emptying and the management of disordered gastric emptying in diabetes. In view of the broad relevance of gastric emptying to diabetes management, it is important that future clinical trials evaluating novel therapies that may affect gastric emptying should quantify the latter with an appropriate technique, such as scintigraphy or a stable isotope breath test.
Graphical abstract